Building Nervous System

Question 1

what are the two parts of the nervous system?

Answer 1

CNS and PNS

Question 2

how many ways can the PNS be spit up? and what are they?

Answer 2

3
how they connect to CNS? cranial or spinal nerves
direction of propagation? afferent or efferent
motor neurone’s target effector? somatic or autonomic (sympathetic or parasympathetic)

Question 3

why are studies of lower species e.g. rates still useful in the understanding of human brains?

Answer 3

this is because all vertebrates share the same basic architecture of the nervous system. there are just systematic changes in brain structures.

Question 4

describe from fish to humans, the different change that happen at each stage

Answer 4

fish - some tubes to carry nerve from distal parts of the body to a rostral point
reptilian brain - nerves sorted into specialised modules e.g. light sensitivity = vision, chemrsensitivity = smell etc. bulge on rostral area of spinal cord, connected to the cerebellum
mammalian brain - hypothalamus allowing reaction to more stimuli. thalamus developed allowing hearing, smell and vision to work together. amygdala and hippocampus allow for crude memory and limbic system generates emotion but they aren’t able to be experienced s it is unconscious
human brain - developed 1.5 million years ago. exposure enlargement of specific areas associated with thinking, planning, organisation and communicating. a larger cortex push cerebellum to current position. skull bones used outwards forming high flat forehead and domed head

Question 5

what are the planes of sections of a human brain?

Answer 5

sagittal
coronal
horizontal

Question 6

how many lobes of the brain are there and what is the main attribute of each one?

Answer 6

4
frontal ; personality
parietal ; abstract mathematical functions
occipital ; vision
temple ; hippocampus

Question 7

what is the function of white and grey matter?

Answer 7

grey matter - which is grey due to its lack of myelin, have cell bodies which are the ‘computer zone’
white matter - a connection between cell bodies. all various computing units can talk to each other, share information, divide work up and checks that conclusions made are reasonable. sends information to specialised computing areas

Question 8

what are gyri and sulci of the brain?

Answer 8

gyri - ridges

sulci - creases

Question 9

what is the cerebellum involved in and what could result from deficiencies in it?

Answer 9

cerebellum is involved in: balance,movement, reading and writing
dyslexia can be due to problems with the cerebellum

Question 10

describe one specialised area of the brain

Answer 10

Brodmann's area - it is a systematic map of the brain based on cell types. for example with speed, there are:
Broca's area (44) - specialised motor area involved in the mechanical production of speech. controls the lips and the tongue
Weirnickes area (22) - involved in grammatical rules for language

Question 11

what are ‘hard-wired’ areas of the brain and give examples of these

Answer 11

hard wired areas are areas where given appropriate conditions, the cells should develop into their genetically preordained form and function.
the motor cortex is for movement and the visual cortex is for vision

Question 12

why has evolution made it essential that humans have specific attributes?

Answer 12

vision
ability to move precisely
faculty of speech
these are all so that humans have an evolutionary advantage over rivals so that these attributes and our genes can be selected for and the species live longer

Question 13

what is the explanation for attributes that have no obvious evolutionary advantages? and give an example of one

Answer 13

playmusic could be an evolutionary advantage as the ability to play music and the intelligence and sensitivity required to play an instrument may be attractive to the opposite sex which means that those genes armoire likely to be passed on

Question 14

how do musicians differ from the rest of the population ?

Answer 14

there is a hook that is in the motor cortex which is an area that controls the hand. in the dominant hand, from a frontal view, this is the shape of an inverted omega in 90% of the population and the shape of a lowercase omega in 10% of the population which is in concert pianists, suzuki players etc

Question 15

what is the reason for an increased size of the hook in musicians?

Answer 15

this is due to the neurones sprouting new connections because they must allow for the signals to get to the correct muscles at the correct time in the correct order.

Question 16

define plasticity

Answer 16

the ability of neurones to create new connections and also destroy old connections in response to new physical demands

Question 17

what makes the brain such a powerful processor?

Answer 17

each neurone can make 1000-10000synapes
the human brain has 10^11 neurones
thus, 10^14 connections are in the human brain

Question 18

describe the overall evolution of the brain

Answer 18

in higher mammalian brains, the development of increasingly complex senses triggered the development of a thin layer of cells on the brain’s surface called the cortex. from which, consciousness emerges. the cortex allows for many neural connections with only a small increase in size

Question 19

what are the three main features of simple cell organisms? give an example of it in action

Answer 19

receptiveness, responsiveness and spontaneity
eg euglena : spontaneous swimming activity, responds to light and the photons transducer by pigment are localised to the eyespot

Question 20

what comes with multicellularity?

Answer 20

specialisation and the appearance of a nervous system

Question 21

give an example of a multicellular organism and describe it

Answer 21

sponges
water flows in through the body wall
water flows out of them through the osculum (large hole at the top)
the flow is controlled by the beating of flagellated cells
and is regulated by the myocytes which are specialised cells tat respond to stretch - can do this becuase of their contractility

Question 22

describe primordial nervous systems

Answer 22

there is an appearance of neurones and the first one is probably a sensorimotor cell. they span from the exterior to the effector cells

Question 23

what is a hydra?

Answer 23

it is a multicellular organism which feed themselves using tentacles which are also used to locomote through the environment by tumbling
there is a derivation of different types of neurones from ectoderm for example motor neurones and interneurones
motor neurone - receive input from true sensory neurones and output - to effector cells and other motor neruones
interneurones lie between sensory and motor neurones and excitation or inhibition allows for more complex responses

Question 24

what are the two types of worms?

Answer 24

segmented and non segmented

Question 25

what do flatworms clustering of neurones show?

Answer 25

- GBCFC - ganglionisation - cephalisation - bilateral symmetry - fasiculation - commissures

Question 26

give an example of a segmented worm

Answer 26

annelids - fusion of longitudinal nerve cords

Question 27

how many neurones anglia do c.elegans have?

Answer 27

302 neurones, 56 glia

Question 28

what kind of nerve cords do c.elegans have?

Answer 28

dorsal, ventral and lateral nerve cords

Question 29

where do most neurones derive from?

Answer 29

from AB cells that have a shared lineage with the hypodermis (skin)

Question 30

describe the formation of a neurone in insects

Answer 30

the neurogenic region is next to the ectoderm (future skin) there is then migration of the neurogenic region as gastrulation proceeds individual neuroblasts delaminate and migrate inward then coalesce.

Question 31

how are glia and neurones formed in drosophila ?

Answer 31

neuroblasts form ganglion mother cells | ganglion mother cells form neurones and glia

Question 32

in drosophila, what does delamination form ?

Answer 32

neuroblasts

Question 33

where is the nervous system on vertebrates?

Answer 33

it is dorsal,

Question 34

what is the hypothalamus also known as? and what is it close to?

Answer 34

the autonomous integrating centre | it is close to the pharynx (the mouth)

Question 35

what is the difference between insects and amphibians in the way that the neurogenic region develops?

Answer 35

the neural cells do not laminate | the neural cells stay as one layer called the neuroepithelium which can often be called the neural plate

Question 36

where does the nervous system of all vertebrates arise from?

Answer 36

the neural plate

Question 37

how do cells become neural precursors differ in insects and vertebrates?

Answer 37

in insects, single cells become neural precursors | in vertebrates, whole groups of cells/sheets of cells become neural precursors

Question 38

where do neural precursors first form in worms, insects and vertebrates?

Answer 38

at the surface. they develop next to the skin on one side and next to the mesoderm on the other side

Question 39

define cell differentiation

Answer 39

the process by which cells become different from each other and acquire specialised properties.

Question 40

what is cell differentiation governed by?

Answer 40

changes in the gene expression, which dictate the repertoire of protein synthesised.

Question 41

what can gene expression of a cell be governed by?

Answer 41

intrinsic (transcription factors) and extrinsic (morphogens) factors

Question 42

how does the neurogenic region arise?

Answer 42

through inhibition of BMP signalling

Question 43

describe the process of BMP inhibition and explain what the homologue for it is in insects

Answer 43

BMP signalling is inhibited by an antagonist - chords BMP and chordin are proteins that have been high conserved through evolution in insects, the BMP homologue is app and the chords homologue is short-gastrulation (sog)

Question 44

what does the dpp/sog network do ?

Answer 44

it broadly dictates dorsal and ventral sides of the body in insects/worms. where dpp is inhibited by sog, the neurogenic region arises.

Question 45

at what point does the neural plate form in insects?

Answer 45

the neural plate broadly forms where dpp inhibits sog

Question 46

at what point does the neural plate form in vertebrates?

Answer 46

the neural plate broadly forms where chordin inhibits BMP (same as in insects but reverse)

Question 47

what is the molecular pathway for the development of a neural plate cell (ectoderm)?

Answer 47

the ectoderm can form either an epidermal cell or a neuronal cell

Question 48

define neurulation

Answer 48

when the neural plate rolls up to form the neural tube, so the vertebrate development progresses

Question 49

what is SMAD 1?

Answer 49

part of a secondary signalling cascade

Question 50

how does the neural plate cell become epidermalised?

Answer 50

BMP must bind to SMAD to phosphorylate it. this would then activate a pathway enabling the cell to become an epidermal keratinocyte

Question 51

what happens to the fate of a neural plate cell in the absence of BMP?

Answer 51

BMP can't activate SMAD1 so SMAD 1 can't enter the nucleus. this means that a different set of transcription factors are unregulated which starts their transcription. this can cause the differentiation of a cell to a neurone.

Question 52

what are the epidermalising transcription factors and what condition is needed for this to happen?

Answer 52

MSX1, GATA and Vent with BMP present cause an epidermis to develop

Question 53

what are the neuralising transcription factors and what condition is needed for this?

Answer 53

XLpok2, SoxD with the absence of BMP

Question 54

how has the understanding about neuralation formed?

Answer 54

though studies on xenopus. following fertilisation, the egg undergoes cleavages and gives rise to 3 hollow balls of cells. 3 germ layers will form called the ectoderm, mesoderm and endoderm.

Question 55

how do we know that the cells in the germ layers are different form each other ?

Answer 55

analysation of the of the transcriptome and proteome in each part, can find 3 big categories of genes then find their proteins and do immunohistochemistry on them to see that the cells are transcribing different proteins.

Question 56

what is produced when transcription factors e.g. Gse are in the 'organiser' ?

Answer 56

in the mesoderm layer, there are specialised mesodermal cells that are induced called the organiser. it expresses special transcription factors and secreted ligands including chordin under the influence of transcription factors such as Gse, the organiser expresses unique secreted products that are all antagonists of the BMP signal

Question 57

what do cells in the organiser turn into?

Answer 57

anterior ectoderm, prechordal mesoderm and anterior neural plate. 1 and 2 become axial mesoderm.

Question 58

define neural induction

Answer 58

the process through which the neural plate forms when BMP antagonists prevent the BMP ligand from stimulating its receptor

Question 59

what is noticed as the neural plate forms the neural tube?

Answer 59

development of the axial mesoderm cells in the organiser differentiate into anterior endoderm adaxial mesoderm. these involute, intercalate and undergo convergent extension after it is induced, dorsal mesoderm involutes and undergoes convergent extension. as it does so, it self differentiates into notochord. convergent extension alters the shape of the developing embryo as these processes occur, the neural plate grows and elongates making the A-P axis and rolls into the neural tube

Question 60

what is noticeable about developing nervous systems?

Answer 60

i developing nervous systems, the anterior end/prechordal mesoderm are in close contact with the pharynx and the ventral forebrain

Question 61

describe the experimental proof for neural induction

Answer 61

in the 1920s, the organiser graft experiment was done by Spemann and Mangold. they grafted the organiser from a donor to a host newt and found that a twinned embryo developed with a complete secondary neural axis. the secondary neural tube was host derived i.e. showing that the neural tissue is induced from the ectoderm in response to signals from the organiser tissue. the exile mesoderm and anterior endoderm were donor derived showing that they had self-differentiated from the organiser.

Question 62

is there any support foremother studies for spemann's organiser?

Answer 62

Henson's node grafted from quail embryo to chick host and also found that a new axis was induceed in the host

Question 63

where does the ability to be neural inducing or the mesodermal dorsalisation come from?

Answer 63

from the ability to synthesise and secrete various BMP antagonists e.g. chordin, noggin, follistatin etc.

Question 64

how were BMP antagonists in the organiser discovered?

Answer 64

by BMP antagonists having all of it's mRNA extracted from organiser cells, reverse transcribing them to cDNA then testing each to look for a gene/protein that would mimic the organiser's ability to induce a secondary neural plate

Question 65

what experiments can be done to prove a molecule is a neural inducer?

Answer 65

-molecule must be expressed the organiser -molecule must be secreted and act on adjacent cells -over-expression of the molecule at an ectopic site should lead to induction of the secondary axis -inhibition of activity should prevent axis formation these types of experiment show that BMP signalling is NECESSARY for neural induction

Question 66

what are the 2 types of experiments that show that BMP antagonists give neural tissue ?

Answer 66

1. express BMP antagonist ectopically | 2. dominant negative experiments with BMP receptors

Question 67

what are the 2 types of experiments that show that BMP antagonists give neural tissue ?

Answer 67

1. express BMP antagonist ectopically | 2. dominant negative experiments with BMP receptors

Question 68

where are the majority of the neurones in the brain?

Answer 68

in the cerebellum and the cortex

Question 69

what are the steps in embryogenesis?

Answer 69

``` CNS PNS Midbrain Hindbrain Spinal cord ```

Question 70

where does all of the nervous site arise from?

Answer 70

the neural plate

Question 71

at what point in development do the main parts of the nervous system become established?

Answer 71

easy in embryogenesis (3-5 weeks in humans)

Question 72

how do we know that all the main different parts of the nervous system begin to be established very early in embryogenesis?

Answer 72

as the organiser/node begins to differentiate into the axial mesoderm, it involutes and undergoes convergent extension and extends under the newly induced neural plate. if development is stopped at this point, and look with molecular markers, can see that the neural plate is expressing markers that are aper confined to the forebrain (early neural plate=anterior in character) this is because BMP antagonists induce neural tissue that has anterior identity. BMP antagonists are made in the early node and in the prechordal mesoderm have different characteristics, providing signals that promote proliferation and growth of neural cells and their 'posteriorisation' the posterior nervous system then develops as the node regresses, posteriorly. axial mesoderm laid down in its wave. it induces proliferation and growth of the neural plate/neural tube. this idea is known as the activation transformation model

Question 73

describe the main concept of the activation transformation model

Answer 73

-neural inducing molecule induce anterior tissue these molecules initially come from the early node/organiser cells but are maintained in the prechordal tissue -other signals from later node/organiser promote growth and posteriorisation ANTERIOR AND POSTERIOR SIGNLAS ACT ANTAGONISTICALLY

Question 74

what is the model basis for the activation transformation model?

Answer 74

- BMP inhibitors from the organiser tissue block the formation of epidermis, ventrolateral mesoderm and ventrolateral endoderm - Wnt inhibitors in the anterior of the organiser allow the induction of head structures - a gradient of caudal factors specify the regional expression of Hox genes

Question 75

where are BMP antagonists and Wnt antagonists maintained?

Answer 75

BMP antagonists and Wnt antagonists are maintained anteriorly

Question 76

what are the caudal factors, where are they expressed and what do they do?

Answer 76

FGF, Wnts and RA are expressed posteriorly and promote growth and posteriorisation

Question 77

how is a core regional pattern in development established?

Answer 77

by placing 2 antagonistic molecules at each end of a forming structure.

Question 78

how is the nervous system along the AP axis?

Answer 78

it is segmented along the AP axis

Question 79

what are the two main models of transforming gradients?

Answer 79

the Lewis Wolpert 'positional information' / french flag model the Alan Turing 'reaction-diffusion' model

Question 80

in drosophila, what is segmental identity controlled by?

Answer 80

homeotic (hox) genes - they provide positional information for the drosophila

Question 81

give 5 facts about the homeotic genes

Answer 81

they are transcription factors they have a shared homeodomain box with DNA - so is a useful marker they specify AP segment identity in dropphila they have been evolutionary conserved many hox genes develop through adulthood

Question 82

how can you experimentally find the function of hox genes?

Answer 82

must KO many hox genes to find the function - because especially in humans and mice, there are many of the same gene

Question 83

what was found when the KO of hox a1 and hox b1 was done?

Answer 83

that they are required to specify rhombomeres 4 (partially) and 5 and the nerves that are normally made from this region

Question 84

what forms at the edge of the neural plate and ectoderm? what is it for?

Answer 84

a specialised border of cells forms at the edge of the neural plate and the ectoderm. it is crucial for neural crest formation and roof plate formation and dorsal neural tube patterning/differentiation

Question 85

what are the different steps for the neural crest formation?

Answer 85

there are 5 steps 1. an early border is established at the interface of the induced neural plate and surface ectoderm. this begins to express specific transcription factors (msx1) thought to be induced at 'intermediate' levels of BMP signalling 2. other signals (wnts, FGFs) act together with msx1 to turn on other transcription factors (Pax 3, Zic 1, Pax 7). the combo of these tfs characterise the neural pate border cell 3. Wnt signals act together with NpB tfs to up regulate further tfs (c-myc, ld, snail etc) that characters neural crest cels. many of these tfs, we know to give stem-like behaviours - proliferation and multi potency 4. in response to c-myc and sox-9, genes that control proliferation and mulitpotency and survival are transcriptionally activated 5. at the same time, neural crest cell tfs upregulate a further set of genes that promote epithelial-mesenchymal cell transit (EMT). neural crest cells delaminate from the border region and begin to migrate.

Question 86

what are neural crest cells also known as?

Answer 86

the 4th germ layer

Question 87

what do neural crest cells give rise to?

Answer 87

a number of different types of cells of the body including scwann and neurological cells and also the sympathetic and parasympathetic system in the PNS

Question 88

what are the different cell types that the neural crest cells will develop dependent on?

Answer 88

the position of origin of neural crest cells timing of generation of neural crest cells (determined by Hox genes) migratory pathway and the signals they encounter en-route or at the target

Question 89

what are the three main pathways of neural crest migration in a chick embryo

Answer 89

superficial pathway - (beneath ectoderm) form pigment cells on the skin intermediate pathway - (via somites) form sensory glia medial pathway - form sympathetic ganglia and cells of adrenal medulla

Question 90

do all neural plate border cells for neural crest cells?

Answer 90

no, a few are retained at the border and form roof plate ells. these are important in the in a step if neuralation and dorsal neural the patterning

Question 91

what happens to the floor and roof plate when a neural tube the is developing into a spinal cord?

Answer 91

a floor plate of non-neuronal cells develops along the ventral midline ad a roof plate f no neuronal cell along the dorsal line

Question 92

where neuronal cells develop nearest to the floor plate?

Answer 92

neuronal cells whose phenotype is not known

Question 93

where do future motor neurones commissars neurones differentiate ?

Answer 93

immediately above the floor plate, in the dorsal region, near the roof plate

Question 94

what do roof plate cells up regulate?

Answer 94

BMPs and Wnts that diffuse into the dorsal neural tube. they induce the expression of a set of tfs (pax 6,7,2 and Lim1) that cause neural tube progenitors to acquire 'dorsal identities'

Question 95

what was thought about BMPs that come from the roof plate?

Answer 95

that they were morphogens that induce different types of dorsal cells.

Question 96

what is actually true about BMPs and Wnts?

Answer 96

recently has been found that they express many different BMPs, each of which induces particular dorsal cell types. they induce different sets of progenitor cells that will ultimately differentiate to distinct neuronal subsets in the dorsal spinal cord

Question 97

what is happening to the axial mesoderm at the same time that the neural plate/early neural tube is forming?

Answer 97

the axial mesoderm forms also and comes to lie just below the ventral midline of the neural tube

Question 98

how do neurones develop around the midline?

Answer 98

neurones develop around the midline, throughout the entire torso-ventral axis (D-V)

Question 99

where are floor plate cells and the notochord located and what do they secrete?

Answer 99

they are located at the ventral midline and secrete morphogens

Question 100

what is the test of if notochord and the floor plate cells diffuse

Answer 100

test by grafting a donor notochord or floor plate to an ectopic position is a host embryo. ask if ectopic floor plate / and ectopic neurones are induced. ectopic floor plate and ventral neurones such as motor errors, induced after a graft of the notochord/floor plate

Question 101

what is the secreted factor made by the notochord and floor plate?

Answer 101

hedgehog which was the name given as the fruit lies look curled up and spiky.

Question 102

what is the hedgehog gene?

Answer 102

a factor that has been conserved in evolution, that has a homologue in drosophila.

Question 103

in the 1980s, what did researchers realise about the conservation of hedgehog?

Answer 103

that hedgehog and shh were conserved between invertebrates and vertebrates

Question 104

where is Shh mRNA expressed?

Answer 104

in the notochord and then the floor plate

Question 105

is Shh protein or mRNA detected more widely?

Answer 105

Shh protein. this is because it appears in a gradient as it diffuses through the ventral neural tube from ventral to dorsal

Question 106

what was the 1st evidence that Shh has a diffusion gradient and can therefore be detected more easily then Shh mRNA?

Answer 106

when an antibody was made against the Shh protein, it was shown to diffuse away from the notochord and floor plate, forming a concentration gradient the ventral part of the neural tube. Shh comes from the notochord and the floor plate and Shh signalling induces expression of transcription factors in progenitors cells. these transcription factors confer ‘ventral’ neural tube identities, so the progenitors will ultimately give rise to cells that differentiate into ventral neurons.

Question 107

how can an ectopic floor plate and ventral neurones be induced?

Answer 107

An ectopic floor plate and ventral neurons are induced after implantation of a shh soaked bead. This is because the bead soaked in purified Shh protein can mimic the effect of notochord/floor plate the transcription factor ‘code’ dictates later differentiation as cells (nerves) differentiate, they move laterally

Question 108

what is the name of the transcription factor that dictates later differentiation?

Answer 108

code

Question 109

what direction do cells move as they differentiate?

Answer 109

they move laterally

Question 110

what is the action of Shh at an early stage ?

Answer 110

it acts to confer a DV pattern of transcription factors on progenitor cells

Question 111

what is the job of tfs upstream?

Answer 111

the transcription factors are the upstream 'master' regulators of particular neuronal fate/identity

Question 112

what patterns the DV axis?

Answer 112

OPPOSING gradients of BMPs and Shh PATTERN THE DV AXIS

Question 113

in what conditions do cells change there fate?

Answer 113

in accordance with their position in the Cartesian grid. this means that different types of neurones differentiate at the same D-V position along different parts of the AP axis

Question 114

give 4 examples of what Shh induces in different parts of the body

Answer 114

-forebrain, it induces hypothalamic neurones -midbrain, it induces dopaminergic neurones in the hindbrain, it induces serotonergic neurones -spinal cord and everywhere else, it induces motor neurones

Question 115

what does the neural tube initially look like and what changes during dark neural tube development?

Answer 115

initially, the neural tube is a single layered neuroepithelium. during early stages neural tube development, some cells continue to 'span' the width of the neural tube. their nuclei migrate back and forth at different stages the mitotic cycle.

Question 116

what are cell that derive from the stem-like neuroepithelium called?

Answer 116

radial glia. they are thought to be the later neural stem cells

Question 117

where does the division of radial glia occur? and what is the product of this?

Answer 117

in the lumen. it can divide to form 2 radial glial daughters or a radial glia and a proliferating daughter progenitor - depending on the plane of division.

Question 118

where do the proliferating daughter progenitors and differentiated cells move into after division?

Answer 118

proliferating progenitors move to the adjacent ,mantle zone (largely picked through various tfs e.g. Nkxx, Pax etc) differentiated cells move away into the marginal zone

Question 119

what is the difference the amount of neurones that can be produced in proneural vs neurogenic mutants?

Answer 119

mutants lacking proneual activity cannot form neurones but neurogenic mutants form too many neuroblasts

Question 120

what is the role of notch and what occurs in its mutants?

Answer 120

it controls the number of cells that from neurones. as it is required to prevent a cell from becoming a neuron. in notch mutants, too many neurones are made.

Question 121

what happens to a cell suppressing notch?

Answer 121

it will become a neuron

Question 122

how does notch work?

Answer 122

locally as it is a juxtacrine signal. it woks on adjacent cells

Question 123

what happens in a fly where there are cutters of cells that have activated pro neural genes

Answer 123

these cells are now competent to become neurones - although only a few actually do

Question 124

what does notch regulate?

Answer 124

lateral inhibition

Question 125

what does notch regulation include?

Answer 125

involves the transmission of an inhibitory signal between a pair/cluster of cells to prevent cells that receive the signal from adopting a particular cell fate

Question 126

what is notch and deltas link?

Answer 126

notch is the receptor for the delta signal

Question 127

describe the steps of lateral inhibition

Answer 127

initially, both cells are equally capable of making and receiving the inhibitory signal. subsequently, a change or bias is introduced - perhaps randomly- so that 1 cell begins to make more inhibitory signal consequently, the second cell receives more inhibitory signal and becomes inhibited.

Question 128

what is needed to stabilise the change of lateral inhibition?

Answer 128

the inhibited cell must be prevented from continuing to send the inhibitory signal

Question 129

what is the importance of balance in notch signalling?

Answer 129

in a pro neural region, notch signalling is balances. a slight imbalance develops and it is then quickly amplified, leading to the development of a neuronal precursor.

Question 130

what is special about the progenitors that don't differentiate?

Answer 130

they have a certain shape they exist as radial glia they provide a pool of undifferentiated cells that are used to build up the nervous system over time in embryogenesis

Question 131

what does the daughter cell of radial glial cells do when it is migrating away?

Answer 131

they use the scaffold provided by its sister to migrate away from the ventricular zone

Question 132

what is the arrangement of the motor system?

Answer 132

its arranged hierarchically

Question 133

what are the different layers of the motor system hierarchy?

Answer 133

- highest level :primary motor cortex - middle level: brainstem - lowest level: spinal cord

Question 134

what is the projection of the primary motor cortex? what does it regulate?

Answer 134

projects directly into the spinal cord via the corticospinal tract regulates the motor tracts that originate in the brainstem

Question 135

what is the pathway of the brainstem and what does it control?

Answer 135

lateral descending system controls distal limbs

Question 136

what does the spinal cord modulate and why can it do this?

Answer 136

modulates reflexes automatisms such as walking as well as many other actions. can do this because it contains neuronal circuits.

Question 137

what neurones have the simplest reflex?

Answer 137

the monosynaptic sensory neurone and motor neurones

Question 138

what is the majority of reflexes in the body ?

Answer 138

polysynaptic with interneurones

Question 139

what is the pathway of the brainstem and spinal cord? what do they control?

Answer 139

brainstem = lateral pathway that controls the hands and arms | spinal cord = direct pathway to the muscles and reflexes

Question 140

what happens if you artificially stimulate the spinal cord,brain stem and the spinal cord?

Answer 140

you would only get twitches [from the speech motor areas (e.g. brooks area) and simple vowel sounds]

Question 141

what is the motor acton of the basal ganglia and the cerebellum?

Answer 141

they receive information from many different areas if the cortex and project to the motor cortex via the thalamus they are aware of the situation a person is and they monitor commands going down to the muscles to make sure that they are appropriate

Question 142

where does the basal ganglia feedback to?

Answer 142

the basal ganglia only feeds back to the motor cortex - subcortical loop

Question 143

where does the cerebellum feedback to ?

Answer 143

the cerebellum mainly feeds back to the motor cortex but can send its signals down to the brainstem, spinal cord and onto the muscles - direct output onto the spinal cord and is an internal subcortical loop

Question 144

what happens if you stimulate different areas of the frontal lobes?

Answer 144

it produces movements on the opposite sides of the body

Question 145

what was done in the mid 20th century to identify motor effects in the frontal lobes?

Answer 145

electrical stimulation was done to identify specific motor effects pf discrete sites in the frontal lobes in different species- especially in humans and primates (wilder penfreid 1891-1976)

Question 146

what are association areas in the brain for?

Answer 146

they are to support the primary areas of the brain

Question 147

what was found about brodmanns area in terms about stimulation eliciting movement?

Answer 147

brodmann's area 4 was found to be an area in which the lowest intestate stimulation elicited movement - in the primary motor cortex

Question 148

where is the brodmann's area located ?

Answer 148

in the primary motor cortex which is located just before the central sulcus (fissure of Rolando)

Question 149

what is the name of the motor cortex first neurones?

Answer 149

the upper motor neurones (UMN) which carry the motor commands own through the brain, brainstem and the spinal cord

Question 150

where does the spinal cord originate from?

Answer 150

not the motor cortex as it is from old areas

Question 151

where is the output of the UMN?

Answer 151

output to lower MN via interneurones

Question 152

what is the role of UMN?

Answer 152

planning, initiating and directing movements

Question 153

where do other UMN originate ?

Answer 153

other UMN originate in phylogenetically ancient motor centres of the brainstem - red and vestibular nuclei, superior colliculus reticular formation - regulate

Question 154

how many UMN pathways are there are what are they? | what is common about them?

Answer 154

two pathways: direct and indirect direct motor pathway - input to lower MNs from axons extending directly from cerebral cortex indirect motor pathway - input to LMN from motor centres in brainstem they both connect to the LMN

Question 155

why do the UMN pathways both connect to the LMN?

Answer 155

because the LMN have a final common pathway

Question 156

what does the basal ganglia do? and what does it connect to?

Answer 156

they provide input to the UMN and connects with the motor cortex

Question 157

what is the role of the basal ganglia?

Answer 157

- helps initiate and terminate movements - suppresses unwanted movements - establishes normal level of toe in muscles

Question 158

what is a disease in which the basal ganglia's inhibited?

Answer 158

Giles de la Tourettes syndrome - they are unable to terminate movements that the rest of us can

Question 159

what is the primary role of the cerebellum?

Answer 159

to step in and correct movement if it is not intended. | controls the activity of the UMN

Question 160

how does the cerebellum connect to the cortex?

Answer 160

connects to the cortex via the thalamus and the brainstem

Question 161

how does the cerebellum correct movement that is not intended?

Answer 161

it monitors movement for differences in intended and actual movements and if there are any discrepancies, it sends an error signal and tries to reduce the discrepancy

Question 162

where is the cerebellum located?

Answer 162

at the base of the brain

Question 163

what is the appearance of the cerebellum?

Answer 163

tight, intricate folds

Question 164

what 3 things did the 'Basic Circuitry' 1967 describe?

Answer 164

the structure of each of the cell types in the cerebellum their synapse connections their electrophysiology

Question 165

what is the name of the 4 parts of the cerebellum?

Answer 165

mossy fibre input granule cells purkinje cells climbing fibres

Question 166

what is the mossy fibre input part of and where is it from?

Answer 166

part of the WM underlying the cortex | from many different regions of the brain and spinal cord

Question 167

what do mossy fibres synapse onto?

Answer 167

granule cells in the bottom (granular) layer

Question 168

what is the proportion of mossy fibre input to granule cells?

Answer 168

granule cells outnumber mossy fibres 50:1

Question 169

where do granule cells send their axons to?

Answer 169

to the top (molecular) layer where they split into two to produce parallel fibres

Question 170

what do the parallel fibres of mossy fibres form?

Answer 170

synapses with purkinje cells

Question 171

what is the name of the largest cel in the cerebellar cortex?

Answer 171

purkinje fibres

Question 172

where are the cell bodies of purkinje cells?

Answer 172

in the middle (purkinje) layer

Question 173

what is the purkinje cells main role?

Answer 173

to be the sole output cells of the cerebellar cortex

Question 174

how many parallel fibre synapses do purkinje cells receive?

Answer 174

around 150,000

Question 175

where do climbing fibres send their inputs?

Answer 175

a single climbing fibre input goes onto each purkinje cell

Question 176

what are climbing fibres?

Answer 176

they are the axons of cellist the interior olive, at the base of the brainstem

Question 177

what do the climbing fibres wrap around? and how many synapses does it form?

Answer 177

the purkinje cell dendritic tree | forms around 1000 synapses - all with the same input signal

Question 178

what is a simple spike in terms of PC firing ?

Answer 178

it is when the PC fires spontaneously of usually about 5o spike/second

Question 179

what can improve the firing rate of the PC cells?

Answer 179

parallel-fibre input can increase this rate to >200 spikes/sec

Question 180

what is a complex spike?

Answer 180

very unusual shape | produced by climbing fibre input

Question 181

why are complex spikes considered reliable?

Answer 181

because whenever climbing fibres fire, PC also fires

Question 182

is there an increased or decreased frequency of firing in terms of complex spikes compared to simple spikes?

Answer 182

there is a decreased frequency of firing compared with simple spikes, so has a little effect on output

Question 183

how does mossy fibre input contrast with climbing fibre input?

Answer 183

they are all wrapped around PC dendrites acts as one enormous synapse low frequency of firing

Question 184

what do unusual circuits do for clinical and experimental observations?

Answer 184

for clinical and experimental observations of cerebellar dagga, can see that it does not cause paralysis but makes movements inaccurate, slow and un coordinated -similar to the effects of alcohol

Question 185

what is important to note about the cerebellums influence on moving the body?

Answer 185

cerebellar damage does not lead to paralysis

Question 186

what is the importance of the fact that cerebellar damage does not lead to paralysis?

Answer 186

this means that other parts of the brain issue movements commands and may carry them out inaccurately

Question 187

what s the role both the cerebellum?

Answer 187

to ensure movements are carried out properly

Question 188

what was Brindley's suggestion?

Answer 188

that the purpose of the cerebellum is to learn motor skills so that when they have been learned, a simple incomplete message can be sent from the cerebrum and will suffice to provoke the execution of the movement

Question 189

what are the two models that have been made to explain the cerebellums role?

Answer 189

the Marr-Albus model

Question 190

what does the Murr-Albus model suggest?

Answer 190

that to learn to make accurate movements, you must have information about what you did wrong an error signal

Question 191

what component of the cerebellum conveys an error signal?

Answer 191

the climbing fibres

Question 192

what do complex fibres change?

Answer 192

synaptic weight

Question 193

what do complex fibres affect on the PC dendritic tree?

Answer 193

all the parallel-fibre synapses

Question 194

what was the rule suggested to explain how complex fibres affect synaptic weight ?

Answer 194

synaptic weight s changed according to the correlation between the parallel fibres signal and the error signal conveyed by the climbing fibres

Question 195

what is the suggested learning rule?

Answer 195

the de-correlation learning tule states that: if there is a positive correlation between the parallel fibres signal and the error signal, the synaptic weight would be low if there is a negative correlation between the parallel fibres signal and the error signal, the synaptic weight would be high

Question 196

when does 'learning' stop?

Answer 196

when there is no longer a correlation between any parallel-fibre signal and the climbing fibre signal

Question 197

where is there support for the de-correlation learning rule? explain it

Answer 197

in long term depression as a paired stimulation of parallel fibres with stimulation of climbing fibres, synapses with parallel fibres and PC become depressed. this is consistent with the error signal idea which was that signals are positively correlated with climbing-fibre signals

Question 198

what is the de-correlation learning rule a version of?

Answer 198

the mean square learning rule and thus is computationally powerful

Question 199

what is the mean squared learning rule used mostly in?

Answer 199

widely used in signal processing( e.g. biomedical engineering, seismology etc)

Question 200

what does the mean square learning rule support?

Answer 200

the cerebellum implements supervised learning

Question 201

what kind of tests have been used to examine the proposed role of the cerebellum in motor learning?

Answer 201

simple motor learning tasks

Question 202

what is the name of the reflex that is sed to stabilise eye movements?

Answer 202

the vestibule-ocular reflex (VOR)

Question 203

describe the VOR

Answer 203

when the head rotates, the eyes move in the opposite direction. this keeps the visual world stable and can be mimicked by looking at a target and moving your head

Question 204

why is VOR so important?

Answer 204

there is a problem when the eye moves relative to the world, the image moves across the retina which blurs vision. this means that visual information is irretrievably lost. this could be bad as you may not be able to see your predator/prey

Question 205

when do we use VOR?

Answer 205

when we walk our heads move and down VOR counter-rotates eyes to keep visual image from moving

Question 206

what are the learned changes in VOR reflex in monkeys?

Answer 206

eyes initially move too far but after some experience and gain of the VOR, it rests and the eyes move an appropriate distance in relation to head movements -- compensating for the altered size of the visual image

Question 207

what part of the cerebellar cortex is involved in VOR adaptation?

Answer 207

the flocculus | inactivation of this region prevents VOR adaptation

Question 208

what things is the cerebellum thought to be involved in?

Answer 208

active sensing, sensory prediction and emotional&cognitive processing

Question 209

what is the basic microcircuitry of the cortex like?

Answer 209

fairly uniform her the entire cerebellum but not identical. this suggests the there is a multiplicity of functions must arise from external connectivity cerebellar zones

Question 210

how is the external wiring of the cerebellum connected to project to a unique set of neural targets?

Answer 210

PCs in a given parasagittal strip of cortex receive climbing fibre input from a unique region of the inferior olive PCs in a given parasagittal strip of cortex project to a unique region of the deep cerebellar nuclei this in turn project to a unique set of neural targets

Question 211

what can be used to predict the sensory effects of the brain?

Answer 211

the de-correlation learning rule

Question 212

why is it not possible to tickle yourself?

Answer 212

because the attenuating signal to tickle comes form the cerebellum and so the cerebellum is what is used to predict the sensory effects of tickling movements - then you would know about it therefore not feel it

Question 213

how to predict the effects of head movements?

Answer 213

cerebellar tuut neurones have been found that respond to passive head movements but don't respond to very similar active head movements. this can also be used

Question 214

how can being able to predict own head movements be an advantage ?

Answer 214

be able to distinguish your head movements from movement thats coming from elsewhere ability to develop a self identity

Question 215

what is the most basic circuit in the cerebellar cortex?

Answer 215

input=mossy fibres. these synapse onto granule cells, whose axons synapse onto PC. PC provide the output of cerebellar cortex. PCs also receive climbing fibre inputs, which behave in a very unusual way

Question 216

what does the basic circuitry of the cerebellum do?

Answer 216

climbing fibres copy error signals about movement inaccuracy. this adjusts the weight of the synapses between parallel fibres and PCs, thus altering PC output in a way that makes movements more accurate. evidence from the adaptation of the VOR consistent with the theory

Question 217

what are the external connections of cerebellar cortex?

Answer 217

each small region of cerebellar cortex has unique inputs and outputs. the cerebellum can influence a very wide range of neural structures, from spinal cord to many areas of cerebral cortex

Question 218

how can the external connections of cerebellar cortex be used for sensory and cognitive functions recently proposed for the cerebellum?

Answer 218

the learning rule proposed for ensuring accurate movements can also be applied to other sensory and cognitive tasks, including the ability to predict the sensory effects of ones own movements

Question 219

define proprioception

Answer 219

the ability to sense stimuli arising within the body regarding position, motion and equilibrium. even with a blind fold, he/she knows through proprioception if an arm is above the head/hanging by the side of the body

Question 220

what does muscle control require?

Answer 220

excitation of a muscle by alpha motor neurones but also continued feedback of information from each muscle to the nervous system at each instant.

Question 221

what information is sent to the brain when muscle control is requires?

Answer 221

muscle length which comes from the spindle | muscle tension and the rate of change of muscle tension development

Question 222

where is information sent from motor neurones going to?

Answer 222

to spinal cord cerebellum and cortex

Question 223

what creates action potentials in the axon?

Answer 223

Group 1 alpha terminal endings are anulospiral and wrapped the equator of both bag and nuclear chain intrafusal muscle fibres. Pulling apart of these coils that initiates action potentials in the axon

Question 224

what information does group 1a sensory endings relay?

Answer 224

Group 1 alpha sensory endings relay information on the dynamic phase of the muscle stretch

Question 225

describe group 2 endings and what information do the sensory endings relay?

Answer 225

Group 2 ending have a ‘flower spray’ terminal ending embedded in the equatorial regions of the bag fibres – but have anulospiral endings largely confined to nuclear chain fibres Group 2 sensory ending relay information on the static phase of the muscle stretch ie its final stretch

Question 226

at what stage during the stretch is the only time that endings respond? when are they free?

Answer 226

Endings only respond during dynamic phase of stretch | Only free after final stretch is reach

Question 227

what useful information does the CNS receive by viewing group 1 and 2 muscles together?

Answer 227

By viewing them together, CNS receives useful information on muscle activity: Group 1: rapid burst of AP when muscle is stetching. Not much at static stretch Group 2: steady state fire rapid Aps. Not much when dynamic stretch is happening

Question 228

what is the problem with muscle spindles if there is no stretch?

Answer 228

they will be useless as Muscle spindles are only useful when they are under tension If there is no stretch- no info will go to the brain

Question 229

How can the system be ore fine-tuned/sensitive when a skilled movement is about to be performed? And less sensitive when not required?

Answer 229

If the itrafusal fibres are exposed to MAOs, (5HT), there will be an increased firing of APs in the gamma motor neurones. This means that the brain is more respondent to that one If the brain is exposed to NA, there will be less APs fired by the gamma motorneurones thereforethe brain isn’t sent much info on these

Question 230

what happens to intrafusal fibres if they are stimulated with 5HT?

Answer 230

By slightly stimulating gamma motorneurones with 5HT: intrafusal fibres can be made slightly stiffer and therefore transmit stretches with greater fidelity

Question 231

what happens to intrafusal fibres if you inhibit gamma motoneurons with NS?

Answer 231

they will be slightly floppier and therefore elastic materials don’t transmit and stretches well, because they stretch Axons in the spinal cord spray muscle spindle intrafusal fibres on structures that we don’t need. Less muscle firing is taken to the brain as we don’t need this information.

Question 232

How can we witness muscle spindles working?

Answer 232

By looking at reflexes

Question 233

describe the tendon jerk reflex | 5

Answer 233

This is a unique reflex because it’s the only monosynaptic reflex Muscle is stretched by a hammer blow in its tendon Primary sensory ending (group 1a) are activated and send Aps along the limb to the spinal cord It has a single synapse with homonymous muscles alpha-motorneurones and produces action potentials in it The muscle contracts in opposition to the stretch and limb jerks as a consequence

Question 234

describe the tendon reflex and jendrasski's manoeuvre | 4

Answer 234

the ‘spill over ecitation’ also effects the gamma motoneurones pool which make the intrafusal fibres ‘stiffer’ and make them more sensitive - -jendrassik’s manoeuvre causes excitation in upper segments of the spinal cord - -excitation spills over to the rest of the spinal cord - -alpha-motorneurones that supply (L1-5) thus brought slightly toward the threshold and so more excitable.

Question 235

describe the tonic vibration reflex | 7

Answer 235

• group 2 afferents fire at abut 50hz when arm is straight • group 2 afferents fire at about 20hz when fully flexed • vibrator applied to tendon ‘drives’ the group 2 afferents in muscle so they discharge at 100hz ie the vibrator frequency - sensory and motor cortex says arm is bent by X amount for brain to register (measured in frequency) - with vibrator, brain registers the vibration so it thinks that the arm is very stretched and so works to try and bend it - reflex works better in females than in males

Question 236

describe the stretch reflex | 8

Answer 236

* most studied spinal reflex-contraction that opposes the lengthening of a muscle * Sherrington (‘father of neuroscience’) showed that the reflex required sensory input from the muscle and a return path to the muscle * Used a new and novel model – the decerebrate cat – surgical transection at the level of the midbrain, between superior and inferior colluculi * Spindle 1a makes excitatory connections on homonymous muscle (muscle and spindle is in 1) and the synergistic muscles (those that ‘help’ the main muscle contraction) * Ia’s also act through inhibitory interneurons that innervate antagonistic muscles * When the muscle is stretched, the Ia firing rate increases * This causes contraction of the homonymous muscle and synergists and relaxation of antagonistic muscles * The reflex therefore tends to counteract the stretch enhancing the springiness of the muscle

Question 237

describe the somatosensory system- where info is processed | what is the central pathway known as?

Answer 237

• Some of proprioceptive information is processed at the level of the spinal cord • Higher level processing occurs in somatosensory cortex (as is touch info) Central pathway is known as DORSAL COLUMN – MEDIAL LEMNISCAL

Question 238

what are the three synaptic relays that are between the periphery and cortex that are in main pathways?

Answer 238

1. Central processes of dorsal root ganglia cells synapse on neurones in gracile and cuneate nuclei in lower medulla 2. Axons from these nuclei ascend in medial lemniscus and synapse on neurones in ventral posterior lateral nucleus of the thalamus 3. Neurones of lateral muscles send axons to primary somatosensory cortex

Question 239

where are the primary and secondary somatosensory cortices?

Answer 239

are in the anterior parietal lobe and the posterior parietal cortex. S2 is deep within lateral sulcus.

Question 240

what does lesioning S1 produce?

Answer 240

Lesioning S1 produces proprioceptive deficits (and ability to discriminate size, texture and shape of objects)

Question 241

where is S1 and what areas does it correspond to?

Answer 241

S1 = in the post central gyrus – corresponding to the Brodmann’s area 1,2 and 3 – and contains 4 subfields area 1,2,3a and 3b

Question 242

why is body representation distorted in the primary somatosensory cortex (S1)?

Answer 242

Body representation in the primary somatosensory cortex (s1) is distorted (homunculus) in which some body parts are over represented (hand, face) whereas other body parts are underrepresented (trunk, leg). This is due to discriminative properties that are more prominent in some territories (hand, face) then others

Question 243

how many neurones does the brain have and how many connections can the brain make?

Answer 243

brain has 10^11 neurones and van all make >10^3 connections so there are potentially 10^14 connections in the brain

Question 244

what are the two theories of specific neuronal activity in the adult organism? who was right?

Answer 244

Weiss (1928) - Resonance theory | Sperry (1939) - Chemoaffinity theory

Question 245

what was Weiis's theory of resonance ?

Answer 245

stochastic (random) and diffuse neuronal outgrowth occurs to all targets followed by elimination of non-functional connections

Question 246

what was Sperry's hypothesis?

Answer 246

that it was directed and specific outgrown that occurs through axons following individual identification tags carried by cells and fibres of the embryo

Question 247

what is the tectum known as in a mammal?

Answer 247

Super colliculus

Question 248

describe Sperry's experiment

Answer 248

cut optic nerve and removal retina. allows just basal axons to grow back. importantly, the regrowing 'red' axons grew through yet ignored the territory normally innervated by the blue axon. this shows that Sperry was right as the axons grew back direct into their right place. however this was done during regeneration

Question 249

what would be expected if the other theory of axon guidance was right ? what is actually observed?

Answer 249

would expect to see random patterns of axons in the embryo but instead, see that patterns of axon growth in the embryo are highly organised, reproducible and stereotyped

Question 250

what are guidance cues?

Answer 250

environmental factors that axons can use to find their correct target

Question 251

what is the anatomy of a growth cone?

Answer 251

the growing tip of the axon cajal proposed to be able to sense cues from within the environment

Question 252

in what organism were easy experiments to identify location of guidance cues done? and why?

Answer 252

on insects - relatively simple nervous system - embryo are easy to observe and manipulate - in the larger insects (e.g. grasshoppers), individual cells may be ablated using lasers

Question 253

what was seen from a detailed analysis of a grasshopper?

Answer 253

identification of almost every neurone in the embryonic nerve cord allowing a map of axon projections to be made

Question 254

what does the reproducibility of axon behaviour show about growth cones?

Answer 254

that growth cones were responding to cues or labels in the environment.

Question 255

in what situations do pathways in axon guidance seem to change?

Answer 255

when specific axons are encountered

Question 256

describe what was fund about G axons and A axons during ablation of P axons

Answer 256

G axon stalls in absence of P axon. not due to lack of axons on which to extend as A axons was still present not due to reduction in numbers of axons as this was not affected when A axons were analysed. this shows that it just be because the G axon growth cone is looking for specific cells on the OP axon - this follows the labelled pathway hypothesis

Question 257

what is the labelled pathway hypothesis?

Answer 257

anxious can selectively fasciculate with other axons axon surfaces carry labels/cues different axon growth cones express different sets of receptors for such cues early axons from an axon scaffold on which later axons can extend establishes axon surfaces a one potential source of guidance cues axon scaffold are important in vertebrates aswell

Question 258

give an example of an experiment where axon scaffolds were important in vertebrates

Answer 258

Ghosh and Shatz (1993): development in subplot neurones subplot neurones project from the core to the thalamus riot to innervation boy LGN neurones if you ablate the part f the subplot early on, before axons extend, then LGN innervations fails in th ablated region

Question 259

what kind of paths do pioneers follow? | eg in grasshopper embryo limb

Answer 259

stereotyped paths and growth cones appear to react at specific points in the pathway e.g. in the grasshopper embryo limb, the pioneer Ti1 growth cones make a specific turn at the limbboundar and then again as it approaches a specific cell, CX1. ablation of CX1 causes the Ti1 growth cone to sell at the other side of the limb boundary implies that there must be a molecular difference in the environment

Question 260

what can CX1 be referred to as?

Answer 260

a 'stepping-stone' or a 'guidepost' cell

Question 261

what dos patterning information from the early embryo predict? give three examples in the forebrain, spinal cord and hind brain

Answer 261

that axon tracts will from forebrain ; axons follow boundaries of domains of patterning gene expression spinal cord = axons are attached to and follow boundaries in the floor plate hind brain ; axons follow boundaries of rhombomeres

Question 262

how many different ways can guidance cues act? | give 2 examples

Answer 262

contact attraction - cell ablations lead to growth cone stalls as if an attractive force has been lost contact repellant - avoid the limb boundary as if it were inhibitory chemoattractant chemorepulsion

Question 263

what is the anatomy of a growth cone?

Answer 263

3 domains: Central : microtubules Traditional : microtubules come into f actin zones Peripheral : f actin

Question 264

what are the different kinds of f actin that makes up lamella and filopodia? are they stuck down?

Answer 264

in lamella, the actin bundles are cross linked into a net in filopodia, the actin bundles are polarised to form larger bundles neither are stuck down - highly motile

Question 265

what is the movement in the central area of a growth cone compared to other domains like?

Answer 265

very random in the centre very organised in the peripheral as there is a continuos flow of f actin from the outside to inside which are recycled which is called the f actin treadmill

Question 266

what is the f actin treadmill?

Answer 266

a continual flow of f actin from the outside to inside which are recycled

Question 267

what happens to tubulin in resting growth cones? does this change in any coiditon?

Answer 267

it is dragged sporadically into the filopodia. this happens more dramatically in the presence of an attractive cue

Question 268

what happens when growth cones come into contact with attractive cues (bead)?

Answer 268

f actin slows and f actin accumulates | this accumulation drags microtubules into the back of the filopodia

Question 269

what would happen to the growth cone if the attractive cue bead was immobile?

Answer 269

the growth cone would reorganise its microtubules completely establishing a new growth direction - the lamella and filopodia reorganise to seek out a new attractive cue

Question 270

can growth cones only be attracted?

Answer 270

no they can also be repelled. this was discovered when mixtures of neurones in culture were found to fasciculate only with their one kind. however, not all due to attractive forces. active repulsion as well as adhesion. the connection is maintained due to signals going onto growth cones and telling it not to join

Question 271

what does dropping a soluble repellent factor into growth cones show? compare this to if there was no reagent

Answer 271

soluble repellent factors dropped into growth cones show that there is less F actin present no reagent = normal growth Expel repellent factor = collapse of the growth cone

Question 272

what are semaphorins? what is their action?

Answer 272

a family of inhibitory guidance cues secreted/soluble semaphoring can cause growth cones to turn collapsing effect is primarily on F-actin

Question 273

how were semaphorins first identified?

Answer 273

biochemical purification of the facts from the retina is responsible for causing the collapse of sensory axons led to the identification of a family of inhibitory molecules now called semaphoring

Question 274

what is the relationship between the strength of adhesion and amount of axon growth? give examples

Answer 274

there is no relationship eg adhesion ; laminin

Question 275

what kind of substrates do growth cones need?

Answer 275

ones that are permissive for growth, not just have the ability to attach

Question 276

give an example of a permissive substrate for growth cones and describe is action

Answer 276

laminin, a growth promoting ECM protein which is localised in the optic nerve laminin does not dictate the direction of axon growth, just gives 'permission' for it to grow there

Question 277

what evidence is there to suggest that laminin is just a permissive factor and not an instructive one?

Answer 277

1. blockade of receptors for laminin slows down the growth of retinal axons, but doesn't change their direction 2. gradients of laminin in vitro don't direct axon growth - in fact it was found that laminin is permissive for growth only when at a specific concentration range. therefore laminin is permissive but not instructive

Question 278

what are permissive and non-permissive substrates also known as?

Answer 278

contact attractants and contact repellants (respectively)

Question 279

what factors can channel axon growth? give an example of it at work

Answer 279

non-permissive factors where axons miss limb-body boundary and so grow abnormally. in mice lacking sema3a, see axons straying into wong territories

Question 280

what is axon growth a balance between?

Answer 280

permissive and non-permissive factors

Question 281

what is an ephrin?

Answer 281

a non-permissive factor that is used in the early patterning and to guide axons

Question 282

what is the name the ephrin and what do they cause? receptor?

Answer 282

Ephs. they cause repulsion between cells which early on, help to compartmentalise the embryo into discrete domains, later they are also used to keep axons out of specific areas in ways similar to semaphorins also used in a special way to create topographic maps they also have a remarkable reciprocal pattern of expression in the mammalian embryo

Question 283

give 3 facts about growth cones

Answer 283

need permissive substrate to grow can be kept out of regions of the embryos by non-permissive factors can be channelled by combinations of permissive and non permissive factors

Question 284

what are commissural axons repelled by?

Answer 284

BMPs which are made y the roof plate

Question 285

what is the role of BMPs in axon guidance?

Answer 285

they take part in determining which types of neurones are specified in the spinal cord. at a later stage, they playa role in pattering agon pathways

Question 286

what does purified BMP7 do to commissural growth cones?

Answer 286

they cause commissural collapse and cells expressing it mimic the repulsion of the roof plate. thus, molecules that were used early on to pattern where specific neurones were born but also used later to guide axons - this is also true for Shh

Question 287

what is netrin and what is it made by?

Answer 287

a secreted protein, similar to laminin which can associate with the ECM. cells expressing the netrin gene can turn commissural axons. made by the floor plate

Question 288

what is expressed in the midline f the vertebrate nervous system - led to by biochemical purification

Answer 288

cloning of the gene encoding floor plate chemoattractant protein

Question 289

do all axons need entrain to reach the floor plate?

Answer 289

no, some axons can reach the floor plate without netrin

Question 290

what does cyclopamine block and what does Smo require?

Answer 290

cyclopamine blocks SHH signalling and Smo is required for SHH signalling. this shows that there are two different pathways leading to the turning of commissures

Question 291

how are gradients of morphogens re-used to shape axon paths?

Answer 291

early patterning information is used to guide pioneer axons. chemoattractant and chemorepulsive molecules work together to guide commissural axons to their initial target, the floor plate

Question 292

what do SHHH and BMPs specify and co-operate with?

Answer 292

they specify neural fate and co-operate with entrain to guide commissural axons

Question 293

what do SHH and BMPs specify and co-operate with?

Answer 293

they specify neural fate and co-operate with entrain to guide commissural axons

Question 294

what is a short-long range guidance cue

Answer 294

sema1 acts as a short range cue and blocking of it's function (with antibodies) leads to axons straying into the wrong areas. blocking sema2 function also disrupts Ti1 guidance in a way that the gradient of secreted sema2 directs the Ti1 growth cone towards the body thus the combo of 4 guidance axons at different stages in their pathways are used in axon guidance

Question 295

what is growth cone navigation broken into stages separated by?

Answer 295

intermediate targets and choice points

Question 296

what are guidance cues used in combinations useful for?

Answer 296

guidane cues used in combinations would generate man more than the theoretical 20000 possible cues

Question 297

what could be the problem if the sensitivity of growth cones to a specific cue change as intermediate targets are encountered?

Answer 297

if the sensitivity of a growth cone to a specific cue can change as intermediate targets are encountered, a guidance cue may be responded to in one part of a pathway but ignored in the next

Question 298

is there any evidence that growth cones are reprogrammed?

Answer 298

axons reprogram when intermediate targets rare encountered. after the transit of the midline,commissural axons lose responsiveness to netrins axons exposed to ectopic floor plate only after crossing the midline is no longer respondent this shows that the sensitivity of axons to floor plate only after crossing the midline is crossed explains, in the hindbrain, commissural axons are able t continue past the floor plate without turning but in the spinal cord, commissural axons turn after crossing the floor plate

Question 299

what are fluorescent dyes useful for tracing?

Answer 299

lineage tracing, membrane tracking and axon tracing

Question 300

at what point do commissural axons become sensitive to repellants?

Answer 300

after crossing the floor plate | i.e. after crossing the midline, commissural axons become sensitive to something inhibitory in the floor plae

Question 301

why don't the commissural axons go straight n after crossing the hindbrain?

Answer 301

the inhibitory molecules in the floor plate are semaphoric and proteins called slits as well as being expressed in the floor plate, they're also expressed in the ventral spinal cord - creating a pathway through which commissural axons grow thus initially these axons must be sensitive to netrin, but not sensitive to the inhibitors. once across the FP, the sensitivities must switch

Question 302

why don't the commissural axons go straight on after crossing the hindbrain?

Answer 302

the inhibitory molecules in the floor plate are semaphoric and proteins called slits as well as being expressed in the floor plate, they're also expressed in the ventral spinal cord - creating a pathway through which commissural axons grow thus initially these axons must be sensitive to netrin, but not sensitive to the inhibitors. once across the FP, the sensitivities must switch

Question 303

how do growth cone sensitivities get reprogrammed?

Answer 303

the roundabout gene encodes receptor for the inhibitory protein SLIT. high levels of the Robo gene are in axons that do not cross the midline. Comm is at low levels but high levels after crossing. over expression of Robo can lead to the appearance of no comm and so axons only grow straight. over expression of Comm looks like there is no Robo and so axons move back and ooh across the midline as the SLIT protein isn't being detected by Robo and so this is not stopped. Comm is in control of Robo as Robo acts if Comm is not working

Question 304

what does the roundabout gene encode for? | when do robo and commissural axons express the most?

Answer 304

encode a receptor for the inhibitory protein SLIT. Robo protein is expressed high levels on axons that do not cross the midline commissures axons initially express low levels but high levels after they cross.

Question 305

give an example of a diffusible attractant and a cell surface repellant

Answer 305

diffusible attractant is netrin | cell surface repellant is SLIT

Question 306

what us the role of Comm in terms of Robo

Answer 306

it is a trafficking molecule - stops Robo from reaching the cell surface meaning that growth cones can't be influenced by the inhibitory signal from SLIT

Question 307

what is the appearance of a cell in which Comm is overexpressed/ forced on the neruones

Answer 307

it will resemble a Robo mutant as the axons will be going across the midline, back and forth

Question 308

what is the vertebrate homolog for Robo and Comm

Answer 308

Robots vertebrate homolog is Robo1but its expressed both before and after crossing the midline Comm doesn't have a homolog vertebrate but there is Rig1 which is expressed before the axon crosses the midline and can block then expression of Robo1 signalling until after the midline has been crossed

Question 309

what happens if there is a loss of Rig1?

Answer 309

there is no commissural axons that reach the midline

Question 310

how can an axon scaffold be put onto an axon?

Answer 310

by homophobic binding done by cell adhesion molecules (CAMs) fr example Fas2 in insects

Question 311

what would happen if there is an attempt to adhere a molecule to one that doesn't usuallyy adhere to others?

Answer 311

aggregation

Question 312

what could a fas2 mutant or over expression of fas 2 cause?

Answer 312

fas 2 mutant would mean no fas2 and so the axons would be defaciculated over expression of fas 2 would lead to novel fasciculation

Question 313

what are CAMs regulated by?

Answer 313

other proteins e.g. BEATS which interfere with CAM-mediated adhesion

Question 314

what is getting off a scaffold on axons controlled by?

Answer 314

Fas2 adhesion over expression of fas2 here would mean that the axons would miss their targets ad fail to fasciculate also BEATS would interfere

Question 315

what are the two types of target selection for axons and scaffolds?

Answer 315

``` discrete targets e.g. 'cellular' in DNS topographic maps ('multicellular') ```

Question 316

describe the process of target selection by discrete targets using ablation, netrins and fas3

Answer 316

in grasshopper and drosophila, ablating specific target muscle, motor axons don't leave the true at appropriate times. this suggests that axons are looking for specific labels on their targets. the use of netrins does the exact same thing as the axons wonder off and don't go the right way to their targets using ectopic netrins causes the axons to innervate wrong muscles fas 3 over expression causes axons to innervate new targets instead this shows that multiple cues are required to be combined in order to an address level

Question 317

state Sperry's 2 theories for the target selection using topographic maps.

Answer 317

speedy and two theories, 1. each axon has a label and there is a complimentary label on each target 2. there is a co-ordinate system which is encoded by gradients of signalling molecules which stamp the latitude and longitude of the cells target. this is then read by complimentary gradients that are expressed in the retinal ganglion cell. theory 2 was proven to be right

Question 318

which of sperrys theories provided evidence for the use of topographic maps in target selection?

Answer 318

the stripe assay showed hat cells from a posterior tectum make a non-permissive factor that repels temporal retinal cells this appears to be due to temporal axons avoiding a repellant factor in the posterior stripes because: 1. the activity was abolished using heat treatments of posterior but not anterior membranes 2. posterior membranes cause temporal growth cones to collapse in vitro the inhibitory fact tuned out to be 2 ephrin's that were expressed highly in the posterior to much lower in the anterior Eph receptors for ephrins A2 nd A5 expressed in the retina high in temporal and low in nasal. this was a counter gradient mice KO of A2 ad A5cause temporal neurones to project axons into the posterior tectum therefore topographic maps are disordered. this shows that non-permissive repellant factors are used instructive to direct growth cones to specific places

Question 319

which of sperrys theories provided evidence for the use of topographic maps in target selection?

Answer 319

the stripe assay showed hat cells from a posterior tectum make a non-permissive factor that repels temporal retinal cells this appears to be due to temporal axons avoiding a repellant factor in the posterior stripes because: 1. the activity was abolished using heat treatments of posterior but not anterior membranes 2. posterior membranes cause temporal growth cones to collapse in vitro the inhibitory fact tuned out to be 2 ephrin's that were expressed highly in the posterior to much lower in the anterior Eph receptors for ephrins A2 and A5 expressed in the retina high in temporal and low in nasal. this was a counter gradient mice KO of A2 ad A5cause temporal neurones to project axons into the posterior tectum therefore topographic maps are disordered. this shows that non-permissive repellant factors are used instructive to direct growth cones to specific places

Question 320

what are neurotrophins?

Answer 320

a family of growth factors in the nervous system

Question 321

describe the discovery of the nerve growth factors (NGF)

Answer 321

it has been discovered by by Bueker (1948) it is a fast growing muscle like cell that might secrete survival factors. implanted sarcomas

Question 322

what was NGF discovered as? - the structure and where?

Answer 322

7s-NGF: a2by2 from submaxillary gland | BNGF = dimer is the active component

Question 323

how can you test if NGF is working?

Answer 323

in a campenot,if NGF is in the chamber, the cells are ok, if not, they die

Question 324

how can you test if NGF is important for outgrowth/survival?

Answer 324

- take away NGF after middle section is grown, the process dies out therefore important in survival - grow only on outside, outgrowth occurs – important in outgrowth

Question 325

does the NGF have tropic or trophic factors?

Answer 325

both tropic (growth direction) and trophic (survival) functions

Question 326

which high affinity receptor does NGF bind to?

Answer 326

``` TrkA = high affinity receptor p75-NTR = low affinity receptor ```

Question 327

what do TrkA an p75-NTR promote?

Answer 327

TrkA promotes growth, differentiation and movement | p75 promotes cell death/survival

Question 328

how long after the initial NGF was found, was another GF found? why is this?

Answer 328

20 years. this is because levels of NTs in the nervous system is lows hard to study biochemically

Question 329

who discovered the first NTs after 20years and what were they?

Answer 329

Yves Alain Barde & George Yancopoulus found: BDNF (high homology wit NGF) NT3&NT4/5

Question 330

what broadly determines whether or not a cell dies? (receptor)

Answer 330

p75

Question 331

give examples of neurones that exhibit different NT dependency

Answer 331

- -placodal sensory ganglia eg nodose prefer BDNF/NT3 - -crest-derived DRGs have subpopulations that respond to NGF BDNF or NT3 - -sympathetics respond to NGF or NT3 but not BDNF - -RUFFINI AFFERENTS, BDNF - -MERKEL NGF, P75

Question 332

what is evidence for the statement that dependency changes over time?

Answer 332

newly born neurones may have no dependency NT3 can support many neurone types early in development arrival at target coincides with new expression of NT by targeted trig mental neurones: need BDNF and NT3 early then NGF then NGF or MSP

Question 333

what are other survival factors for animals that don't have NTs?

Answer 333

Glia-derived neurotrophic factors eg GDNF supports midbrain dopaminergic neurones cytokines eg ciliary neurotrophic factors CNTP hepatocyte GF macrophage - stimulating protein MSP

Question 334

what are target derived factors critical in the formation of?

Answer 334

monosynaptic stretch reflex between motor neurones (MNs) and proprioceptive Ia sensory neurones (PNs)

Question 335

what do MNs innervating the triceps and pecs develop compared to MNs innervating the CM/LD? and whites this controlled by?

Answer 335

MNs innervating the triceps and pectoral muscles develop monosynaptic connections directly with PNs whereas MNs innervating the cutaneous maximus (CM) or latissimus doors (LD) receive polysynaptic input from interneurones. controlled by GDNF secreted by CM and LD which turns on the tf Pea3 in MNs. Pea3 KO results in MNs innervating CM/LD that have the dendritic morphology of Tri and pec innervating MNs and aberrant proprioceptive connection ---- i.e. turns them into having 'monosynaptic connections'

Question 336

what does circuit completion rely on?

Answer 336

target feedback. this determines the final afters of both dendritic and axonal connections

Question 337

what does NT3 induce the expression of?

Answer 337

the tf Er81 by Ia proprioceptors.

Question 338

what does KO of er81 lead to?

Answer 338

KO of Er81 leads to failure of the Ia central projection to reach the ventral horn and form monosynaptic connections with the appropriate MNs.

Question 339

what are some non-target derived effects?

Answer 339

``` many neurones themselves synthesis NTs lack of synaptic input can cause loss of target neurones -eg somatosensory barrels anterograde transport of NTs -eg WT3 in retinal ganglion cells paracrine effects -ealry DRG in single cell cultures release NT3 -promotes differentiation ```

Question 340

what are the determinants of survival of a neurone?

Answer 340

- primary determinant is whether or not there is co-ordinated electrical activity pre and post synaptically - altering activity leads to changes in neurone survival

Question 341

what happens if there is a block to the post neuromuscular junction?

Answer 341

there will be no competition between the synapses so fewer losers i.e. more MNs survive

Question 342

what converts electrical activity into survival?

Answer 342

the more active a synapse, the more neurotrophic it takes up by membrane recycling

Question 343

how does membrane recycling link to target tissue mass?

Answer 343

the greater the target mass, the more NT available

Question 344

where does cell death occur?

Answer 344

everywhere | the production of viable neurones and the degeneration of them is seen at all levels of the NS

Question 345

what is the name of a programmed cell death?

Answer 345

apoptosis

Question 346

what does death during synaptogenesis reflect?

Answer 346

reflects competition, make more; kill more

Question 347

what is neurone survival correlated with?

Answer 347

neurone survival is correlated with the amount of target tissue

Question 348

how does cell death occur?

Answer 348

most cells die through apoptosis. this is programmed cll death that is an active process.

Question 349

what is apoptosis inhibited by?

Answer 349

actin myosin D (transcription) | cycloheximide (protein synthesis)

Question 350

what cleans up the mess made once apoptosis is complete?

Answer 350

macrophages plus neutritic disintegration and removal

Question 351

what do caspases cleave proteins involved in?

Answer 351

inhibiting apoptosis DNA repair cell cycle nuclear structure

Question 352

describe the intrinsic pathway of apoptosis

Answer 352

DNA damage and p53, injured mitochondrion, Cytochrome C release and binding of Apaf1, aggregation of Apaf1 and binding of procaspase 9 then activation of procaspase 9 leading to a caspase cascade.

Question 353

describe the intrinsic pathway of apoptosis

Answer 353

killer lymphocyte, aggregation and cleavage of procaspase and molecules activated caspase 9 leading to a caspase cascade

Question 354

what genes are requires in C elegans for apoptosis? what is the anti-apoptotic gene? what is it's mammalian homologue?

Answer 354

- in C. elegans, ced-3 and ced-4 required - cells must express both ced-3 and ced-4 to die - anti-apoptotic genes eg ced-9 (bcl-2) - mammalian homologues = caspases

Question 355

what promotes neurone survival?

Answer 355

targets secrete a factor requires for pre-synaptic neurone survival

Question 356

what happens if there is a withdrawal of NGF from sympathetic ganglion neurones?

Answer 356

SGN have p75NTR, TrkA and low TrKC Low NGF + BDNF (p75NTR, TrkB) = apoptosis --blocking with anti-p75NTR an rescue the kid NGF - induced apoptosis --ie BDNF activating p75NTR is necessary and sufficient for apoptosis in SGNs.

Question 357

what evidence is there to support the idea that p75NTR is necessary and sufficient for apoptosis?

Answer 357

p75-NTR KO mice have a higher neurone number (21000) compared to an adult wt (17000)

Question 358

what do neurones need for apoptosis?

Answer 358

the presence of the correct NT and the absence of the wrong one

Question 359

what activates p75NTR and what does this lead to?

Answer 359

proNGF strongly activates p75NTR - this can lead to apoptosis so the levels of enzymes to cleave PRO NGF = important too growth cones can release cleavage enzymes

Question 360

describe the synthesis and sorting of brain-derived neurotrophic factors in a typical neuron

Answer 360

proBDNF synthesised if it can bind carboxypeptideE the there is regulated secretion before intracellular cleavage. if it can't bind carboxypeptideE, leads to consecutive secretion before intracellular cleavage. this leads to release in dendrites/axons (if not cleaved, released as protein)

Question 361

how does the likelihood of a neurone surviving during development change?

Answer 361

the programmed cell death of neurones during development = activity dependent neurones that are stimulated by excitatory NTs survive no stimulation - neurones may die

Question 362

what does activation of glutamate receptors induce?

Answer 362

local activation of glutamate receptors induce the production of neurotrophic factors (BDNF & NGF) in the post synaptic neurone

Question 363

where are neurotropic factors released and what do they activate?

Answer 363

neurotrophic factor - released locally at the active synapses, activates receptors in the presynaptic neurone

Question 364

what is the determinant of survival of MNs?

Answer 364

initially, MNs innervate a single muscle fibre normally, this is then reduced by competition to a single MN innervating a single fibre (MN fires at the same time fibre contracts) blocking activity leads to reduction in synapse loss --more polyneuronally innervated muscle fibres

Question 365

what converts electrical activity into survival?

Answer 365

if there are 2 axons innervating the same muscle fibre which produces BDNF, the winner out of the 2 would be the one that has local stimulation to convert proBDNF into BDNF. this ensures survival. the loser would be if no proBDNF=converted. this triggers its retraction and if it has no other NMJ's, then apoptosis would be triggered. this proves that apoptosis during development = activity dependent. neurones that are stimulated survive

Question 366

why does where receptors are matter?

Answer 366

``` hippocampus NMDA receptors synaptic and non-synaptic STAU evokes apoptosis reduced by blocking GABA (bicucculine) synaptic receptors = anti-apoptotic extrasynptic receptors= proapoptotic ```

Question 367

why does where receptors are matter?

Answer 367

``` hippocampus NMDA receptors synaptic and non-synaptic STAU evokes apoptosis reduced by blocking GABA (bicucculine) synaptic receptors = anti-apoptotic extrasynaptic receptors= proapoptotic ```

Question 368

why do axonal growth cones follow attractive and repulsive cues?

Answer 368

follow cue to target tissue

Question 369

what does the growth cone do when it contacts the post synaptic membrane?

Answer 369

it stops growing, differentiation in pre-synaptic terminal | at the same time - target cell specialises to create post-synaptic site

Question 370

what is needed in order to form functional synapses?

Answer 370

the correct receptors being expressed synapses a the correct location correct part of the membrane to different into the synapse receptors that match the target the correct number of synapses made -this can vary from 1-10,000 per neurone - i.e. synapses need to be made and stabilised

Question 371

outline synaptogenesis of NMJ

Answer 371

on approach, motor axon differentiates into motor nerve terminal of contact point schwann cells gap the junction muscle forms the post synaptic apparatus

Question 372

what are the morphological changes in synaptogenesis?

Answer 372

small vesicles at the presynaptic membrane narrow cleft between pre and post synaptic membranes post synaptic membrane appears thickened (PSD). cf newborn

Question 373

what are changes when a growth cone turns into pre synapse?

Answer 373

1. filopodia retraction, tight junctions formation 2. membrane + Ex cell glycoproteins added 3. pre-synaptic vesicles, dense ECM, PSD, receptors accumulate in the cleft

Question 374

when does synaptogenesis occur?

Answer 374

when axons reach their target which is very variable

Question 375

how does the process of synaptogenesis differ in vitro and in vivo?

Answer 375

synapse density increases for 1 month at post natal dio cf mouse olfactory bulb increase is at post natal week 1 in vitro, synapses can form on contact in vivo, there is an extended period

Question 376

what dictates synapse sites?

Answer 376

approaching growth cones 'talks' to targets site availability may be restricted - astrocytes may cover cell body- dendrites free (olive) post synaptic cells may have pre-prepared sites - e.g. cadherin/other adhesion molecules

Question 377

where do AChRs cluster and what does this involve?

Answer 377

initially, ACh receptors are present at moderate levels - myotube surface innervation ; AChRs cluster in post synaptic membrane this clustering involves both redistribution of AChR proteins and localised synaptic synthesis ofAChRs

Question 378

whats one principle feature of synaptogenesis?

Answer 378

aggregation of neurotransmitter receptors AChRs cluster in developing myptubes glycine, GABA and glutamate receptors also cluster

Question 379

what evokes clustering?

Answer 379

denervated and destroyed muscle \NMJs from where 'synaptic' basal lamina persists a proteoglycan was identified and called agrin

Question 380

what is AGRIN?

Answer 380

it is a proteoglycan that is responsible for triggering clustering

Question 381

describe agrin

Answer 381

agrin is purified from T.California clusters AChRs has multiple binding sites for the ECM/adhesion made by motor neurones and muscle

Question 382

describe the mechanism of Agrin action

Answer 382

Again bind to muscle specific kinase (Musk) this activates Raspyn Musk KO mice are agrin insensitive

Question 383

describe the maturation of post synaptic apparatus

Answer 383

shape= junction changes from simple oval plaque to a pretzel likes of branches topography = junctional membrane changes from a flat sheet to invaginated surface with gutters and folds ECM: changes to basal lamina over the AchR rich membrane + cytoskeleton apparatus that are under it Channel function = AchR subunit composition Molecular partitioning = ion and ligand-gated channels segregate into discrete alternating domains

Question 384

describe what happens when the presynapse differentiates?

Answer 384

growth cones express Frizzled, FGFR2, Neuexin eg granule cells express ; Wnt7a, FGF23, Neuroligin contact ie sigalling recruits vesicles,synaptic proteins to from pre-synaptic site

Question 385

how many inputs do mature muscle fibres receive?

Answer 385

initially muscle fibres receive multiple inputs in mature muscle, one input per muscle fibre every muscle fibre is innervated nonrandom : competition

Question 386

how doe the number of climbing fibres per purkinje cell change during development?

Answer 386

during development - 4 CF's per cell | mature cerebellum -1 CF per purkinje cell

Question 387

what is synaptic refinement? and connection focusing?

Answer 387

focusing CF re-organisation initial contacts on soma mature contacts on dendrites b) immature inputs are not segregated

Question 388

how is the choice of transmitter chosen during synaptic refinement?

Answer 388

choice of transmitter may depend on environment e. g. parasympathetic/sympathetic neurones (MP) - -most SYMP are ADR+ - -most PARA are ACH+ transplantation - -PARA -> SYMP = ADR+ - -SYMP -->PARA =ACH+

Question 389

how do excitatory synapses in the CNS and NMJ build synapses?

Answer 389

using activity dependent and independent mechanisms to build a synapse acquisition of presynaptic release machinery + post synaptic NMDA receptors but if no additional input, they remain silent because they lack sufficient AMPA receptors activity recruits AMPA receptors the post synaptic domain to activate synaptic activity

Question 390

what are the silent synapses in developing and mature systems like?

Answer 390

intact, non functional synapses seen in NMJs activation like LTP in the mature hippocampus?

Question 391

what are the two types of memory?

Answer 391

declarative and non-declarative declarative - memory about certain facts/objects/events non-declarative - skills that are learnt throughout our lifetime

Question 392

what are the two types of NTs used in memory?

Answer 392

excitatory - glutamate: depolarisation | inhibitory - GABA - hyperpolarisation

Question 393

what are voltage gated calcium channels regulated by?

Answer 393

the position of calcium channels and where it is closer or further from the synaptic vesicle release closer = more sensitive therefore less depolarisation would be required for it to cause a release

Question 394

what are the proteins that are important for synaptic vesicle release?

Answer 394

synaptobrevin SNAP25 Syntaxin when they interact with each other, the synaptic cosine is driven very close to the membrane therefore modifying these could regulate synaptic vesicle release

Question 395

what is synaptogamin and what does it do?

Answer 395

it is a calcium sensor. without this, woudnt have calcium channels there is a high number of these, all with different calcium sensitivities regulates the amount of calcium released

Question 396

what are the 3 different kinds of vesicles in and around the active zone?

Answer 396

1. readily releasable pool - very close to the active zone - released as soon as Ca enters 2. proximal pool - function is to restore the active zone (before readily releasable) 3. reserve/resting pool - function is to restore the proximal pool

Question 397

what is the speed of release in the readily releasable and proximal pool like?

Answer 397

The speed of release in the readily releasable pool is very fast the speed of release in the proximal pool to becoming the readily releasable pool is very slow

Question 398

what is the problem with there being overstimulation of synaptic vesicle in memory?

Answer 398

overstimulation of the synapse would have little/no readily releasable vesicles - this is because the synapse has changed its responsiveness to the stimulus very important form of plasticity which is involved in different forms of depressions/habituation

Question 399

what are the two types of neurotransmitter receptors?

Answer 399

metabotropic - coupled with a G protein | ionotropc - fused with ion channel - this responds to glutamate

Question 400

what are the 3 different kinds glutamate receptors?

Answer 400

NMDA receptor - more selective for calcium, opens ad there is an influx of calcium. contains a magnesium bound so mis depolarise memo to remove and open AMPA receptor - Na/K selectivity - binds glutamate, opens, Na influx - depolarisation mGlut receptor - Gq pathway (cAMP) --> PLC ([Ca]increases)

Question 401

what are advantages to studying the memory capabilities of invertebrates?

Answer 401

bigger neurones size - easy to patch (clamp) circuit complexity - simpler (smaller) number of neurones less temperature dependence - can work in many temperatures mapping (developmental, genetics, stereotypy)

Question 402

what are the simple types of memory?

Answer 402

habituation - decrease of responsivity of sensory system when there is a lot of stimulation - usually when its not harmful/useful sensitisation - NS starts to respond to the same stimulus more than once

Question 403

give 4 examples of habituation in humans

Answer 403

habituation of eye blink reflex of repetitive non-harmful stimulus presentation (e.g. living on a noisy road) of visual attention of emotional response

Question 404

what is the model organic for studying memory in simple organisms?

Answer 404

aplysia - they are happy being cool

Question 405

what are the two important organs in apylasia?

Answer 405

siphon - important for location | Gill - important for breathing

Question 406

describe the experiment of testing habituation in apylasia

Answer 406

touch the siphon 10-15 times for 10-60 second intervals | this reduces its reflex which occurs at the abdominal ganglion synapse

Question 407

where can habituation happen?

Answer 407

- synapse between sensory terminal and sensory neurone = desensitised - synapse between L7 and muscle = desensitised - synapse between sensory neurones and L7 = desensitised

Question 408

what does habituation result from?

Answer 408

reduced synaptic strength

Question 409

what is an experiment that shows the sensitisation in apylasia?

Answer 409

there is an increased gill withdrawal reflex evoked by tail pinch/shock involves pre-synaptic input from sensory neurones - serotonin and Protein action

Question 410

what is the mechanism of sensitisation - what model could be used?

Answer 410

the simple bear model pka phosphorylates and inactivates K+ channels longer depolarisation means more vesicular release

Question 411

how does the apylasia learning relate to associative learning

Answer 411

pavlovian conditioning weak siphon touch (s) paired with strong shock (US) = increased CS timing is critical

Question 412

describe the mechanism of paired stimuli effects in lesnring through simple Bear's model

Answer 412

calcium influx (CS) synergises 5HT effect (US) when you stimulate sensory neurones with a conditioned stimulus, you have depolarisation which leads to an increase in calcium in the cytoplasm when you stimulate L29, there is serotonin release when you pair these 2 stimuli, you get an additional activation of adenylate cyclase (more cAMP molecules)

Question 413

what are the mechanisms of sensitisation and learning?

Answer 413

multiple intracellular signalling pathways varying activation thresholds pre and post synaptic long-term involves the nucleus (gene expression)

Question 414

who conducted lymnae study in 2006 showing feeding behaviour?

Answer 414

Kemenes

Question 415

what is non-synaptic plasticity?

Answer 415

experience-dependent changes to synaptic efficacy not based directly on synaptic changes

Question 416

describe the single trial associative learning experimental model

Answer 416

there is an attractive feeding source present (US - sucrose) and a neutral stimulus (CS; amyl acetate). with no learning, it doesn't cause feeding behaviour after pairing them, one trial later, the snail shows feeding behaviour to amyl acetate

Question 417

what is the cell type that permits feeding behaviour?

Answer 417

serotonergic cerebral giant cells (CGCs). they contact many cell types and permit feeding but are not involved in feeding behaviour. they are a gatekeeper they stimulate the muscle to contract during feeding, they spike continuous. paired neurones of CGC = function is to permit feeding behaviour. if it fires, feeding behaviour happens. if it does not fire, it doesn't happen

Question 418

what was found 24 hours after the single trials of lymnae?

Answer 418

there was a large depolarisation in neurones 24 hours later and the resting membrane potential increased by about 10mV but this was the only change observed. this shows that after training, CGC neurones depolarise more

Question 419

what is the problem with the lymnae study in that depolarisation only happened 24 hours later?

Answer 419

in the first 24 hours, there was no change in depolarisation in GCC neurones yet they had learned the behaviour. this could mean that the depolarisation was random and is not actually needed for learning. suggests that CGC neurones are involved in long term memory - not short term.

Question 420

how can you show the the depolarisation of the membrane is both necessary and sufficient?

Answer 420

1. hyperpolarise neurones in traded animals | 2. depolarise neurones in untrained animals

Question 421

what does amyl acetate show in a trained tissue prep?

Answer 421

amyl acetate triggers fictive 'imaginary' feeding behaviour in trained tissue prep: produces bursts from feeding network behaviour 'untrained' amy acetate doesn't show anything

Question 422

what does single spikes and depolarisation trigger in CGC neurones? what are the main conclusion that can be drawn about the CGCs role in memory?

Answer 422

single spikes in depolarised CGCs trigger a response depolarisation increases calcium presynaptically amy acetate triggers increased activity in feeding behaviour pathways when CGC is depolarised the main conclusion is that long term memory is partially encoded for at a site distant from to the neurone producing a behaviour

Question 423

who invented the hebbian synapse?

Answer 423

Donald Hebb

Question 424

what disease is the hippocampus susceptible in getting early?

Answer 424

Alzheimers

Question 425

how many different neurones does the Entorhinal cortex contain?

Answer 425

3 different neurones -dentate gyrus -CA3 neurones - main output of the hippocampus -CA1 neurones CA3 neurones also have 2nd axon that projects to area that has CA1 neurones. synapse between CA3 and CA1 neurones 0 highly studied

Question 426

describe the LTP phenomenon

Answer 426

usually CA3 to CA1 synapses high frequency stimulus produces along lasting potential shows input specificity shows co-operativity (co-incidence), which does not need HFS two pathways converging in the same target can both be strengthened if they fire together one pathway may be quite weak associative

Question 427

how does LTP occur?

Answer 427

LTP could occur by pre-synaptic changes evidence suggests often a post-synaptic event most indicates a critical role for Ca2+

Question 428

what causes co-operativity in LTP?

Answer 428

co-operativity may be a result of NMDA properties NMDA receptors have a voltage dependent magnesium block so, NMDA receptors need to be indirectly pre-activates by a separate depolarising input

Question 429

if an essential aspect of LTP occurs army, does it require proteins?

Answer 429

some essential aspects of LTP occur early and do nt require protein synthesis some are late and do

Question 430

describe early phase LTP

Answer 430

NMDR-mediated calcium increases and activates calmodulin Kinase 2 PSD protein (2-5%) multiple catalytic subunits autophosphorylation and constant activation triggered by calcium n LTP phosphorylation enhances AMPA currents KO/ inhibition studies are conflicting

Question 431

what is AMPAfication ?

Answer 431

the delivery of ready made AMPA receptors to the synapse

Question 432

describe late phase LTP

Answer 432

long term storage needs protein synthesis take effect about 1 hour after initiation cAMP signalling may be critical

Question 433

is LTP memory?

Answer 433

there are different types of synapses and LTP mossy fibres - CA3 LTP is nonNMDA and mainly presynaptic high transmitter release calcium activated/cAMP mediated perforant path - dentate gyrus does not use camk11 LTP varies in non-hippocampal areas e.g. cortex

Question 434

what are the different types of memory within LTP?

Answer 434

the hippocampus is mainly new and declarative in function | episodic, semantic, spatial recognition

Question 435

what is the relationship between LTP and memory?

Answer 435

inhibiting LTP inhibits some memory formation APS and Morris water maze - time critical effect mutations of camk11, NMDARs, cAMP pathways all affect aspects of learning drugs to enhance memory also enhance LTP e.g. nootropics however AMPAKines in alzheimers - poor success

Question 436

is LTP necessary and sufficient for memory formation ?

Answer 436

it is only necessary for some memory formation but its not sufficient

Question 437

how long is the LTD phenomenon? an where is it?

Answer 437

it is an actively evoked., long lasting reduction in synaptic efficacy examples in the cerebellum where there is low EPSP in purkinje fibres and in the hippocampus where i occurs in the same synapse that LTP occurs in

Question 438

what are the two types of LTD and how do they differ?R

Answer 438

depotentiation - removal of previous potentiation - i.e. wipes out effect of LTP if LTD is triggered LTD de novo - had no previous potentiation and so has no synapses with them

Question 439

what does it mean for LTP to be hebbian ?

Answer 439

hebbian means that its homosynaptic like LTP | non-hebbian means that's heterosynaptic and so doesnt require pre-synaptic activity.

Question 440

what are the general mechanisms for LTD induction?

Answer 440

often requires NMDA receptors, but not always (e.g. in a case in the cerebellum) often evoked by low frequency stimulation but not always often requires calcium influx and activation of serine/threonine phosphatase (unlike LTP; protein kinases) often involves glutamate, but also diffuse transmitters e.g. 5HT and endocannabinoids, like anandamide, released post-synaptically to inhibit pre-synaptic transmitter release

Question 441

what is the input and the output of the cerebellums LTD circuitry?

Answer 441

input -- +ve mossy and climbing fibres | output -- negative purkinje fibres

Question 442

what is the route of transport for mossy fibres and climbing fibres in LT?

Answer 442

mossy fibre - granule cells (parallel fibres) - purkinje cells climbing fibre --purkinje cells

Question 443

what happens in LTD when climbing fibres have been activated?

Answer 443

theres an increased depolarisation of the purkinje cells

Question 444

describe purkinje synapses from LTD and PF

Answer 444

a paired pf and cf input to a single purkinje cell evokes LTD it is int specific the Albus Mar model suggests that cf input indicates a motor error and so weakens the pf;p synapse

Question 445

what does LTD in the cerebellum help us to do?

Answer 445

it helps us to learn motor skills

Question 446

what are the cerebellar LTD mechanisms?

Answer 446

doesn't involve NMDA receptors metabotropic Glu-R, AMPA-R and voltage gated calcium channels needs co-incident activation of both intracellular signalling pathways PKC phosphorylates AMPA Glu-R subunit (on sights different to in LTP) reduces currents by endocytosis AMPA-R internalisation triggered by phosphorylation endocytosis inhibitors preventLTD therefore prevents memory formation

Question 447

what is Bienenstock, Cooper, Munro (BCM) theory about LTD?

Answer 447

the synapses are carve when the rest of the cell doesn't become weakened

Question 448

where does LTD occur? what is its function?

Answer 448

at the CA3 - CA1 synapse with low frequency stimulation (1-5Hz) LTD can reverse a previous LTP depotentiation it is calcium dependent but so is LTP

Question 449

what does the likelihood of inducing LTP or LTD i the hippocampus depend on?

Answer 449

the amount of NMDA receptors. if there is a lot, will be LTP receptors if there is little-no NMDA receptors, LTD is induced because LTP requires NMDA receptors but LTD doesn't

Question 450

what is the phosphatase/kinase balance in the hippocampus like for LTD?

Answer 450

small increase in calcium from NMDA-R triggers more phosphatase action and reduces AMPA-R efficacy large increases activate more protein kinases, which increase AMPA-R efficacy and/or other proteins

Question 451

does LTP+LTD =memory?

Answer 451

no. close but not quite

Question 452

describe an experiment which shows that LTP and LTD are not the only aspects contributing to memory formation

Answer 452

marmosets (monkeys) were in 3 groups nd put into 2 environments. 2 groups were in an enriched environment (interesting) and 1 group was in a boring environment. looked at the shapes of all different neurones in the post-synaptic goudons. monkeys in interesting environment had a higher number of dendritic spines and there was a change in the synapses, the umber of the, and position etc. this shows therefore that memory is not just about LTP/LTD

Question 453

what function is the hippocampus involved in? how do we know this?

Answer 453

involved in new memory formation damage causes anterograde (inability to form new memories), not retrograde (inability to recall precious memories) amnesia its also important in spatial memory

Question 454

how do associated or poorly associated sets of inputs affect synapses?

Answer 454

Associated sets of inputs strengthen synapses but poorly associated sets weaken synapses, including those that may have been strengthened before

Question 455

what was shown in free-moving was about affects to the LTP/LTD?

Answer 455

Novel environments and novel objects / arrangements influence LTP/LTD respectively

Question 456

what do stressful stimulus promote? LTD or LTP

Answer 456

LTD

Question 457

where is long term memory ended? and whites the main job of the hippocampus?

Answer 457

Long-term memory may be encoded outside the hippocampus – its main job is to make new associations and pass them on for storage if appropriate.

Question 458

what controls the excitability neurones?

Answer 458

excitability is funsatmental to their functions | vast majority of neurones communicate chemically

Question 459

who first described the chemical communication of neurones?

Answer 459

Sherrington (1906)

Question 460

what do we need to transmit and control signals in neurones?

Answer 460

``` transmitters receptors ECM other neurones Glial cells need sodium channels to ope and get an AP ```

Question 461

how do sodium channels open?

Answer 461

more positive membrane potential. need a negative resting membrane potential (-70mV) you need to establish the resting membrane potential

Question 462

what do we need t establish the resting membrane potential?

Answer 462

pumps/transporters - regulate ionic gradients channels - (Na2+,Ca2+) K+ - terminate AP-return cell to resting membrane potential

Question 463

how can you generate complex repsonses in membranes?

Answer 463

you can generate complex responses by changing what channels, transporters are expressed

Question 464

how is excitability developed (during embryogenesis)?

Answer 464

resting potential falls during development new channels,new pumps glia (astrocytes) increase, concentration of potassium outside decreases from 35-3mM action potentials appear early - e.g. xenopus from cosureof the neural tube

Question 465

what are the changes the happen during development?

Answer 465

resting membrane potential becomes MORE NEGATIVE input resistant FALLS membrane time constant (MTC) falls MTC depends on resistance and capacitance

Question 466

why does MTC change during development?

Answer 466

neurones get baggers can store more charge e.g. ferret -FGN

Question 467

what are the 2 principle routes for action potential development?

Answer 467

1. long calcium dependent then short, sodium dependent - ->tetrodotoxin-resistant - ->eg mouse dorsal route ganglion, RohonBeard cells 2. short sodium dependent - ->eg mouse spinal cord

Question 468

what are Rohan-beard cells and what is important for them

Answer 468

mechanosensory cells of lower vertebrate dorsal spinal cord | appearance if delayed rectifier K+ channel important

Question 469

what is the difference between a rectifier and a delayed rectifier?

Answer 469

a rectifier is a channel that only allows current through one way a delayed rectifier is a channel that opens some time after its voltage threshold has been reached outward delayed K+ rectifiers also the change out of neuroses after an AP appearance of such channels shortens the AP

Question 470

describe calcium waves

Answer 470

Ca2+ waves and spikes waves influence process growth and differentiation e.g. mouse spinal cord neuron expression of enkephalin e.g. myocyte expression of AChR e.g. xenopus expression of GABA

Question 471

what do adult GABA receptors do?

Answer 471

adult GABAa receptors are inhibitory: GABAa inotropic GABAb metabotropic

Question 472

what is the action of GABAa in development ?

Answer 472

in development, GABAa depolarise immature neurones have high chlorine concentration inside chlorine efflux causes sodium and calcium influx via VACs increased expression of K+/Cl- co-ransporter KCC2 (out) little decreased expression NKCC1 (in) switches effect to hyper polarising

Question 473

what is the GABA receptor development itself?

Answer 473

``` receptor subunits change hippocampus GABAa(a1 green, a2 red) ```

Question 474

why is regeneration important?

Answer 474

there is a large number of traumatic injuries in the peripheral nerve (300,000 per annum in Europe only) spinal cord injury stroke - due to lack of blood supply

Question 475

what is the regeneration capacity lower vertebratees like? give an example

Answer 475

lower vertebrates have a high regeneration capacity | eg newt regenerates whole limb if it has been damaged - the bone, muscle skin and nerve!

Question 476

what is the xenopus tail regeneration triggered by?

Answer 476

BMPs. heavily dependent on signalling molecules BMP and Notch

Question 477

describe the idea that there is a window of refractory activity

Answer 477

tadpole, cut tail at 42 hours, will regenerate,at 48 hours, will regenerate nut at 47 hours, will not!

Question 478

can newts regenerate without nerves?

Answer 478

newts can have regeneration without nerves and form non-neurogenic limb production

Question 479

what is regeneration in higher animals like?

Answer 479

regenerating the PNS myelinating axons covered in schwann cells covered in connective tissue - endoneurium grouped into fascicles covered by connective issue - perineurium etc

Question 480

what are the 3 nerve injury classifications?

Answer 480

neuropraxia - preserve nerve conduction distal to injury axonotmesis - preservation of nerve itself neuretmesis- whole nerve = severe

Question 481

what happens to the nerves when it is a very severe injury?

Answer 481

more severe=more nerves would be affected - lose all connections and complete separation of whole nerve

Question 482

what is the process of regeneration of peripheral nerves?

Answer 482

cell death is more likely closer to soma -proximal axon and soma- reorganisation and re-expression of immature features, e.g. tubulins – distal axon: Wallerian degeneration. axons close to cell soma are okay but al the distal parts are quickly damaged important to get rid of dying axon to start making a new one

Question 483

what are the effects of nerve injury/cell death on denervated muscles?

Answer 483

muscle atrophy AChR reversal to embryonic MusK increase extrema input can help prevent atrophy- over time, decreases in calibre of muscle fibres if not, system tried to cause sprouting

Question 484

what does regeneration involve?

Answer 484

mitosis of schwann cells (supply GFs) formations of bands of Bungner (row of schwann cells to guide axons re-growth along dividing schwann cells sprouting - fibre of adjacent motor neurone may try to innervate it to preventive loss of function

Question 485

describe what happens when there is a spinal cord injury

Answer 485

Sprouting followed by failed regeneration, and degeneration Cysts and glial scars form Recovery of connections difficult

Question 486

why is recovery of spinal cord injuries so bad?

Answer 486

due to inhibitory myelin there is an inhibitory area in the spinal cord that doesn't exist in the PNS neurones try to avoid oligodendrocytes CNS neurones avoid oligodendrocytes in vitro removing myelin/oligos improves regeneration auto immunisation to myelin proteins improved regeneration

Question 487

why is recovery of spinal cord injuries so bad?

Answer 487

due to inhibitory myelin there is an inhibitory area in the spinal cord that doesn't exist in the PNS neurones try to avoid oligodendrocytes CNS neurones avoid oligodendrocytes in vitro removing myelin/oligos improves regeneration auto immunisation to myelin proteins improved regeneration myelin proteins eg nogo-a inhibits axon growth

Question 488

what is the myelin protein that inhibits axon growth?

Answer 488

Nogo

Question 489

what are the different kinds of Nogo in its family?

Answer 489

Nogo-a 200kd in olivos and developing neuorones Nogo b 55kd,in many cells Nogo c 25kd, muscle

Question 490

which nogo do fish and salamanders lack and what doe this do for them?

Answer 490

fish ad salamanders lack nogo a | KO or antinogo decreases the inhibition (partially)

Question 491

what evidence is there to support/oppose the idea that nogo inhibits regeneration?

Answer 491

supporting = putting CNS axons into the PNS environment leads to regeneration. shows that the CNS environment (which has NOGO in it) is the problem opposing = there is no correlation between nogo receptor and regeneration capacity transplanted hippocamal neurones grow axons into myelin much myelin is removed b macrophages after damage

Question 492

what is wallerian regeneration and what is the difference between it in the PNS and the CNS?

Answer 492

wallerian degeneration is the removal of debris it is quicker in the PNS then in the CNS this could be due to myelin

Question 493

are astrocytes responsible for poor regeneration?

Answer 493

could be because they create a tissue which is inhibitory and fibres and it hard to overcome it is found in all parts of the CNS they proliferate at lesions;: glial scars, jumbled astrocytes, attachments to astrocytes impairs region secrete inhibitory condroitin sulphate proteoglycans (SPGs)

Question 494

what is spinal cord bridges used for?

Answer 494

for the repair biological (sural) and artificial bridges may be used filled with growth factors, ECM, synthetic matrix etc

Question 495

what is spinal cord bridges used for? what are they filled with?

Answer 495

for the repair biological (sural) and artificial bridges may be used filled with growth factors, ECM, synthetic matrix etc

Question 496

give 4 methods clinical ways to repair the body cells/neurones after injury and what are there success likelihoods

Answer 496

1. transplant foetal cells a. Parkinsons - may have undesired side-effects. easy trials with conflicting resul b. Huntingtons - little integration/improvement of graft survival 2. transplant h-ESC-derived progenitors - great potential, prep for clinical rials 3. transplant umbilical cells 4. Transplant autologous NS stem/other cells

Question 497

give 4 methods clinical ways to repair the body cells/neurones after injury and what are there success likelihoods

Answer 497

1. transplant foetal cells a. Parkinsons - may have undesired side-effects. easy trials with conflicting resul b. Huntingtons - little integration/improvement of graft survival 2. transplant h-ESC-derived progenitors - great potential, prep for clinical rials 3. transplant umbilical cells 4. Transplant autologous NS stem/other cells - stem cells in the adult brain

Question 498

how can you prove that there are new cells being made in the brain using timidine?

Answer 498

inject timeline labelled with its isotope into animal and can see where this is being made -- found in brain, new cell proliferation so new DNA was made therefore new ells are made in the brain

Question 499

what animal shows that new neurones are made in the brain? and in which areas is that possible?

Answer 499

male songbird from SVZ-HVC show that new neurones were produced as an old animal learned to sing 2 areas in the brain that have it: -area of forebrain SVZ (olfactory epithelium) [less established in humans] -area of hippocampus (dentate gyrus)

Question 500

what do rodents have that humans don't in terms of regenerative capacity?

Answer 500

rodents have more of the ability to regenerate. the olfactory ensheathing cells have the ability to encourage regeneration and is fairly accessible to be studied.

Question 501

what are the 3 types of stimuli that the visual system is tuned to recognise?

Answer 501

food predator mate

Question 502

what is the morphology of the sensory neurone defined by?

Answer 502

its function

Question 503

what are the three ways in which the visual system processes level organisation?

Answer 503

positive feedforward - use excitatory neurotransmission negative feedback - from 2nd layer to 1st layer negative feedforward

Question 504

what can the optic nerve be referred to as? and how does it respond to light?

Answer 504

the information bottleneck | by changing spike rate (increasing or decreasing it)

Question 505

what are the 2 parts of the visual field and what are their roles?

Answer 505

the right and left visual field. the right hemifield activates the left brain and vice versa. in the right visual field, it activates the left part of the retina which both project onto the left part of the brain. information here goes to the lateral geniculate nucleus and the superior colliculus

Question 506

what is the main function of the retina?

Answer 506

image acquisition

Question 507

what is the role of the superior colliculus and the lateral geniculate nucleus?

Answer 507

superior colliculus - responsible for focusing the eye lateral geniculate nucleus - main info, sends info and projects int to the primary visual cortex where information processing occurs. (processes the visual information)

Question 508

what are the 2 main pathways in the cortex?

Answer 508

ventral 'what' object feature stream - inferior temporal - responsible for processing object identity. starts in the V1 cortex along to the inferior temporal cortex dorsal 'where' spatial location stream -posterior parietal - responsible for space related problems

Question 509

whites the function of the pupil, lens and fovea?

Answer 509

the pupil regulates the amount of light that falls on the retina lens focuses image on fovea fovea is the part of the retina with the highest visual acuity. the rest of the retina has a smaller acuity and contains primarily rods but in the flea, the rods are around the fovea rather than in it so they have a much larger sensitivity to light

Question 510

where are photoreceptors located in the eye and why?

Answer 510

they are on the opposite side of the eye so when light comes in to an active photoreceptor,it must first travel through the entire tissue light doesn't go through the entire retina, goes through specific cells that are transparent- others are white

Question 511

what cells does light go through in the retina?

Answer 511

muller cells which is a type of glial cell

Question 512

what is the basic layout of the retina?

Answer 512

consists of 3 neurones and 2 layers of synapses. 1st layer is a layer of photoreceptors with 4 types of cells (rods and 3 types of cones - activated by different colours) 2nd layer is a layer of bipolar cells (inner nuclear layer) 3rd layers a ganglion cell layer - these collect information and send it to the optic nerve

Question 513

what are the two types of synapses in the visual system?

Answer 513

inner and outer plexiform layers | contain synapses of cells that belong to each of the three layers of the retina

Question 514

what are the two interneurones within the 2 layers of the synapses in the retina?

Answer 514

their function is essential and they shape the response of photoreceptors, bipolar cells and ganglion cells inhibitory - mostly glycenergic/gabaergic

Question 515

what do horizontal and amacrine cells send feedback/feedforward to?

Answer 515

``` amacrine cells - send feedback to bipolar cells ; inhibit them send feedforward to ganglion cells DONT CONNECT TO PHOTORECEPTORS horizontal cells - send feedback to photoreceptors send feedforward to bipolar cells DO NOT CONNECT TO GANGLION CELLS ```

Question 516

when are rods and cones most active?

Answer 516

rods - active at dim light cones - active at bright light photoreceptors respond to flashes of light by hyper polarisation (decrease in membrane potential)

Question 517

what do photoreceptors and bipolar cells have in common?

Answer 517

they both don't spike

Question 518

whites a ribbon synapse and what receptor do they relate to?

Answer 518

ribbon synapses are what is able to keep vesicle release permanent in photoreceptors. these constantly release glutamate in the dark

Question 519

do photoreceptors have all or nothing action potentials or graded potentials?

Answer 519

they had graded potentials and do not spike

Question 520

what do photoreceptors release?

Answer 520

glutamate. when the light goes up, the release rate goes down and vice versa

Question 521

where do bipolar horizontal, amacrine and ganglion cells receive input from?

Answer 521

bipolar and horizontal cells receive input from photoreceptors in the OPL ganglion and amacrine cells receive input from bipolar cells the IPL

Question 522

which cells hyperpolarise and which ones depolarise in response to light?

Answer 522

the majority of bipolar cells are OFF cells. hen light goes on, these cells hyper polarise because photoreceptors release less glutamate therefore there is less activation of bipolar cells some of the bipolar cells are ON cels. when light goes on, these cells depolarise

Question 523

what is the sign inverting synapse in ON bipolar cells? explain the action of metabotropic receptors

Answer 523

instead of expressing ionotrpic glutamate receptors, instead express metabotropic glutamate receptors. these are not coupled to channels directly. instead - they are coupled to a G protein these cells have a channel that is activated by cGMP. when the metabotropic receptor is activated, the amount of cGMP decreases in the cytoplasm of dendrites which leads to the closure of the channel so the channel hyper polarises. so when the photoreceptors are active, the amount of glutamate decreases and the metabotropic glutamate receptors are less active which leads to depolarisation

Question 524

what receptors do OFF and ON cells express?

Answer 524

OFF cells express glutamate receptors (EXCITATORY) | ON cells express metabotropic glutamate receptors (INHIBITORY)

Question 525

define the receptive field?

Answer 525

an area in the retina (or space) which when illuminated activates a visual neurone

Question 526

what is the centre surround organisation of the RF? give an example

Answer 526

illumination of the centre and the surround of the retinal feels, leads to responses in the opposite polarities eg in an OFF cell, if you shine light in the middle of the cell, the cell depolarises, if light is shined on the outside, the cells are hyperpolarised

Question 527

what kind of cells have centre surround organisation in the receptive field?

Answer 527

bipolar and ganglion cells | activation with spot and annulus leads to responses in different polarities.

Question 528

where does the central surround organisation of the RF of bipolar cells come from?

Answer 528

from inhibitory feedback from the horizontal cells

Question 529

where do bipolar cells receive their input and output?

Answer 529

inout directly from photoreceptors located in the centre of the RF and indirectly via horizontal cells

Question 530

what are ganglion cells designed to respond to in terms of their centre-surround organisation?

Answer 530

illumination differences that occur with the receptive field is what ganglion cells are designed to respond to. not illumination of the whole receptor field

Question 531

why do we need colour vision?

Answer 531

helps in object recognition. for insects that need to find flowers to survive, wouldn't be able to do so without colour vision

Question 532

what is used to activate different bipolar cells?

Answer 532

there are three types of cones with different spectral sensitivities These types activate different populations of bipolar cells

Question 533

what is the distribution in the retina like?

Answer 533

dorsal (upper) part of retina = green cones ventral (lower) part of retina = blue cones wave of light comes in then to opposite sides - green wave at the bottom and blue wave on top

Question 534

what are the layers of the lateral geniculate nucleus and describe them

Answer 534

``` 6 layers monocular input layers alternate input from each eye P and M ganglion cells remain segregated organised retinotopically ```

Question 535

what is the role of the thalamus station?

Answer 535

thalamus 'relay' station = somehow processes info from eye to brain

Question 536

what are the layers of the LGN?

Answer 536

C, IP, IP, C, IP, C (1,4,6) receive input from the contralateral eye (2,3,5) receive input from the ipsilateral eye

Question 537

what do the M and P cells from the layers 1-6 in the LGN do?

Answer 537

1 & 2 = M cells - position 3-6 = P cells - processing information about object identity all sent to different layers of the visual cortex

Question 538

how many connections do the ganglion cells make with the LGN projection neurones?

Answer 538

1:1 connections

Question 539

are there any similarities or differences between the receptive fields of the LGN neurones and that of the retinal ganglion cells?

Answer 539

SAME - they are the same shape and size DIFFRENT - 60% of synaptic input from cortex 'back propagation' local interneurones in LGN

Question 540

describe the process of object recognition

Answer 540

a few neurones in the higher cortical areas fire | stimulation of the same neurones cause perception of the same object

Question 541

what is object recognition in orientation invariance?

Answer 541

can recognise objects that are in orientations that we have not previously seen the in before

Question 542

what is scale invariance in object recognition?

Answer 542

the fact that the brain can recognise objects independently other size

Question 543

what is the hierarchical model of object recognition?

Answer 543

1. Categorisation (e.g. a human, an animal, a vehicle etc.) 2.View-invariant object detection (particular person, a car) 3.Detection of objects from one point of view (e.g. a person from a front) 4.Detection of object parts (e.g. face) 5.Detection of combination of edges and contours 6.Detection of edges there is an increase in stimulus complexity from 6-1

Question 544

what are the two key features of the cortical structures?

Answer 544

layering - send their projections to different parts of the brain columns - (ocular dominance, orientation and direction) and blobs

Question 545

which inputs in the lateral geniculate nucleus do P and M cells send projections to?

Answer 545

P send projections mainly to 4CB and 4A | M send projections mainly to 4Ca

Question 546

what do resident cells do?

Answer 546

receive inputs from some layers and project the to different parts of the cortex

Question 547

what is the purpose often different layers in the LGN?

Answer 547

they help to process information as they each come from different ares

Question 548

what is the columnar organisation of the cortex like?

Answer 548

ocular dominance orientation (direction) column Blobs (colour)

Question 549

how can you test ocular dominance columns in the visual cortex?

Answer 549

inject radioactive proline in one eye or inject radioactive glucose in the cortex and stimulate one eye with light each column receives input from either the ipsilateral or contralateral eye - helps with 3D vision

Question 550

what are the 3 types of cells in the V1 cortex?

Answer 550

simple complex hypercomplex

Question 551

what do blobs respond to?

Answer 551

respond to different colour dyes - have neurones that are specifically trained to do this

Question 552

why re receptive fields of LGN neurones aligned?

Answer 552

to build an elongated simple cells receptive field

Question 553

have the receptive fields that are downstream of V1 been studied?

Answer 553

they increase in complexity and so are difficult to stay. theres 2 approaches: guessing or using a computational model to predict their response to many images

Question 554

what is the Jennifer Aniston neurone?

Answer 554

it is a specific neurone that fires in response to seeing a familiar face. this examplee is that people who have seen her before would have a neurone that fired to her, her profile and even someone who is known to be associated with her. formerly known as the grandmother cell

Question 555

what is the problem with theoretical models that were designed to study hierarchical models?

Answer 555

they are still poor in scale - and orientation invariance do not take into account feedback from higher cortical areas ('top down regulation') need experimental validation which is difficult, because one need to record pre and postsynaptic responses

Question 556

what are the main methods of studying vision?

Answer 556

psychophysical methods and illusions lesions ad other ways to silence neurones or parts of the brain anatomical studies and morphology (to study connections between neurones FMRI, electrophysiological recordings and imaging modelling and theoretical stimulations

Question 557

what are the model organisms used to study vision?

Answer 557

``` humans (+) can give verbal feedback (-) not easy to express due to long generation time cant put electrons on them - ethical considerations primates lower mammals (cats, rodents) lower vertebrates (zebrafish) invertebrates (drosophila) ```

Question 558

where in the brain do lesions, brain imaging techniques and multi electrode recordings happen?

Answer 558

lesions - take certain parts of the brain - can see if vision is impaired whole brain imaging techniques - see which part of the brain is activated for a particular task multi electrode recordings in different brain areas

Question 559

give an example of the effects of a lesion in a patient

Answer 559

patient following a stroke, had difficulty perceiving certain forms of motion, object recognition and colour perception were in tact

Question 560

what is fMRI used for? in moving and stationary dots

Answer 560

FMRI is a good way to study brain areas involved in visual processing as it can detect which parts of the brain take in more oxygen and glucose. there are 2 stimuli (moving and stationary). fMRI response is higher for moving dots then it is for stationary dots which shows that the MT+ cortex is involved in seeing moving stimuli

Question 561

who was the first to describe the morphology of ganglion cells?

Answer 561

Canal 1892

Question 562

what kind of cell is used to describe the morphology of neurones in the brain?

Answer 562

fluorescent cells. they can drive the expression of fluorescence to label each thing to visualise structural differences and can dissect its circuitry

Question 563

explain the process of patch clamping

Answer 563

use electrode with holes in it goes close to the cell but doesn't penetrate it creates a negative pressure so forms a tight connection between the membrane and the patch clamp (by creating suction) higher resistance leads to a higher quality recording can either record from just one cell or entire area (+) in control of wha is happening inside the cell e.g. can add a backer and choose what it effects or even use a fluorescent dye that labels morphology of a specific dye so you can gather information of the structure / morphology of a wide range of cells

Question 564

what is the role of GCaMP3?

Answer 564

reports changes in neuronal calcium concentration and therefore, neuronal activity fused 2 proteins (M13 and CaM, which interact in the presence of calcium the entire molecule is stabilised and in the correct conformation due to calcium concentration increasing as the molecule is more active expressing this in individual neurones can lead to you seeing when neurones are active

Question 565

what are the benefits and disadvantages of using GCaMP3?

Answer 565

recording the activity of many neurones can record simultaneously the input and output of a particular neurone (circuit reconstruction) can easily target a particular neuronal type (-) image is taken every 4 seconds at a high frequency which takes too long very slow imaging faster with electrophysiology

Question 566

what is the depolarisation by light called and explain it?

Answer 566

channelrhodopsin a light activation channel (blue light 480nm). when its activated, the channel opens, increase in sodium going in, leads to a depolarisation in the neurone and so causes a spike.

Question 567

what is the hyper polarisation by light called and explain it?

Answer 567

halorhodopsin (yellow light [570nm]) there is a chloride influx. when the channel opens, due to light shining on it - the chloride influx leads to hyperpolarisation

Question 568

describe one disease of the eye and the cause and treatments

Answer 568

retinitis pigments (most abundant cause of blindness) no efficient treatments (no prevention) the cause is the death of a retina (degeneration), no more photoreceptors leads to the rest of the retina degenerating treatment = artificial retina - retina (mostly for retinas pigments) and the visual cortex (when the optic nerve didn't develop or is destroyed)

Question 569

why is it important to activate the artificial retina as early as possible in the visual pathway?

Answer 569

retina performs complex computations | different ganglions

Question 570

how can you activate an artificial retina?

Answer 570

by electric stimulation of the channelrhodopsin and halorhodopsin (activation by light)

Question 571

describe the process of delivering channelrhodopsin/halorhodopsin to bipolar cells to see if it restores vision

Answer 571

there is a layer of ganglion cells that are only accessible part to put the electrodes on and so have access to photoreceptors halorhodopsin expressed in retinitis pigments retina using yellow light, could activate it, these parts expressed glutamate response of ganglion cells in the retina with degenerated photoreceptors - key properties of ganglion cells are the same -- start spiking when they see yellow light due t receiving input so cells decrease fitting rate when there is no light (OFF cells) therefore the key difference of having ON/OFF cells in ganglion cells install present. centre surround organisation of RGCs in intact: increased size of light spot (covering entire field), stops responding direction selectivity is intact. (direction= spike, opp=no spike). using this method, can restore the function/vision. i clinical trials ATM -