Embryology of nervous system Flashcards
(112 cards)
1
Q
What are the prosencephalon and mesencephalon and rhombencephalon?
A
- Specializations along the rostro-caudal axis
- Development centers at the rostral end of the neural tube
- Primary cerebral vesicles
- Go on to develop into five secondary cerebral vesicles
2
Q
How do each of the primary cerebral vesicles form the 5 secondary cerebral vesicles?
A
• Prosencephalic vesicle - segments from one into three
○ Telencephalic vesicles are paired vesicles cranially
○ They expand off of the more caudal diencephalic vesicle
• Mesencephalic vesicle - stays the same and does not further segment
• Rhombencephalic vesicle - splits into more cranial metencephalon and the more caudal myelencephalon
3
Q
The secondary cerebral vesicles and their lumens correspond to what adult nervous system components?
A
• Telencephalic vesicles
○ These are paired and they form the cerebral hemispheres, each with a lateral ventricle
• Diencephalic vesicle
○ Thalamus, hypothalamus, subthalamus, epithalamus
○ Lumen of vesicle will give rise to third ventricle which communicates with each lateral ventricle through the foramina of monroe
• Mesencephalic vesicle
○ Mesencephalon (midbrain)
○ Lumen - aqueduct of sylvius
• Metencephalon
○ Pons and cerebellum
○ Lumen of rhombencephalon will become 4th ventricle which communicates with subarachnoid space
○ Paired foramina of Luschka and midline foramen of Magendie
• Myelencephalon
○ Medulla
○ Lumen of rhombencephalon will become 4th ventricle which communicates with subarachnoid space
○ Paired foramina of Luschka and midline foramen of Magendie
4
Q
The lateral ventricles come from what?
A
• Lumen of telencephalic vesicles
5
Q
What are the names of the 5 secondary brain vesicles?
A
- Telencephalon
- Diencephalon
- Mesencephalon
- Metencephalon
- myelencephalon
6
Q
What is the initial event that appears to establish the axis of the embryo?
A
- Mammalian egg is symmetric, but sperm entry breaks symmetry
- Blastomere getting the sperm entry point tends to divide first forming the embryonic pole
- Rostrocaudal axis occurs with implantation, ICM side of blastocyst enters uterine wall
- The end that leads implantation is the caudal end
7
Q
What are the early signalling events that helps the embryo grow along an axis?
A
- Signal from implanting trophoblast (nodal) induces a head organizer in the anterior hypoblast cell
- Secreted factor cerebrus inhibits nodal and creates a gradient of nodal signaling (rostrocaudal in orientation)
- Forms primitive knot, hensens node/primitive node
8
Q
The primitive rod-like notochordal process is formed by what?
A
- Portions of the primitive mesoderm coalescing and forming the notocordal process
- This is just below the primitive node initially and grows caudally
- This structure is initially hollow
9
Q
What is the “normal” destiny of the neurenteric canal?
A
- It normally regresses and the notochord coalesces into a solid tube
- However, this process and fail and cause a neurenteric fistula or neurenteric cyst
10
Q
What is the neurenteric canal?
A
- The hollow notochordal process fuses with the endodermal layer
- As this fusion occurs there is a brief period of time where the amniotic cavity and yolk sac are in communication through the notochordal process
- The communication is called the neurenteric canal
11
Q
The release of Sonic Hedgehog is due to what structure and what is the result?
A
- The notochord releases Shh
- Induces the overlying ectoderm to divide rapidly
- Forms a thickened cell mass called the neural plate
- Neural plate will then crease and form neural groove
- Eventually the groove will become a tube, which becomes the adult nervous system
12
Q
What are the anterior and posterior neuropores?
A
- The small unroofed portions or openings at each end of the neural tube
- Part of the lengthening of the neural tube is when the neural folds come together in a “zipper like” fashion, progressing rostrocaudal toward each end
- The “zippering” doesn’t quite finish and that results in the two ends having neuropores
- The do eventually close as well
13
Q
When does secondary neurulation take place?
A
- 28-32 days
- Aggregate of undifferentiated cells at caudal end of embryo (caudal cell mass) develops
- It develops vacuoles as it enlarges
- Ultimately makes contact with central canal of neural tube from primary neurulation
- Caudal cell mass gives rise to conus medullaris and filum terminale
14
Q
What is a NTD less severe than a myelomeningocele but caused by the same general proces?
A
- Lack of a vertebral arch in a given area
- The neural tube does close but it is not completely surounded by the sclerotome
- The sclerotome makes up the vertebral arch, so that doesn’t form
- Usually there is a mark in the skin or a dimple where this lack of fusion took place
15
Q
What went wrong if there is a myelomeningocele?
A
- Incomplete closure of the neural tube
* Plaque of neural tissue contiguous with epidermis
16
Q
Where do the adult structures: conus medullaris and filum terminale come from in the embryo?
A
• The caudal cell mass of secondary neurulation
17
Q
What might cause the failure of forebrain structures to develop?
A
- This is called anencephaly
- The neural tube does not close at the anterior neuropore
- The neuropores are the last areas in the “zippering” of the nerual tube to fully fold over and close
18
Q
What dietary intervention has been key in reducing neural tube defects?
A
- Periconceptional folic acid supplements
- 400 micrograms of folic acid daily through the first trimester of pregnancy
- If they have previously had a NTD pregancy then 4mg daily 1 month before conception is recommended
19
Q
What is a key molecular mechanism to determining an axis upon which the embryo devleops?
A
- A concentration gradient of morphogens secreted by anterior cells vs. posterior cells
- The concentration gradient gives rise to regional expression of different developmental control genes along the axis of the morphogen gradient
- Wnts, FGFs and retinoic acid are the major players for the AP/RC axis
20
Q
What are the important morphogens for the development of the AP/RC axis?
A
- Wnts, FGFs and retinoic acid are the major players for the AP/RC axis
- Cerebrus and dickkopf are secreted by the anterior visceral endoderm and they promote forebrain differentiation
21
Q
What factors, when secreted, promote forebrain differentiation?
A
• Cerebrus and dickkopf are secreted by the anterior visceral endoderm and they promote forebrain differentiation
*this is happening in the context of the RC/AP axis being developed in the embryo
22
Q
What are the names of genes that are super fundamental in AP patterning of nervous tissue?
A
- Homeobox genes
- First discovered in Drosophila embryonic patterning
- Best characterized in development of rhombencephalon
23
Q
What are rhombomeres?
A
- 8 morphologically distinct elements within the developing rhombencephalon
- They are repeating units that end up differentiating similarly, but distinct based on region
- Under the main control of homeobox genes
- Between rhombomeres, cells will differ in terms ofmorphology, axonal trajectories, NT synthesis, NT selectivity, firing properties and synapse specificity
24
Q
What is the result of Hox gene expression varying along the AP axis of the neural tube?
A
- The result is a differential gene expression pattern overall in the different rhombomeres
- The programs of differentiation they trigger will vary according to position along axis
25
What is RA, and what are RAREs?
* RA is retinoic acid, a vital secreted factor for the deveolpment of the AP axis in neural development
* RA is membrane permeant and bindes to RARs or Retinoic acid receptors
* The receptors will invfluence gene expression along RA response elements in the DNA, or RAREs
* RA is highest in concentration around the posterior positions
* Too much RA means too much posterior structures at the expence of anterior ones
* Thus, RA can toxicity can mess up the embryo something fierce
26
What is the neuroepithelial layer?
* The walls of the neural tube initially possess a pseudostratified layer of primitive ectoderm known as the neuroepithelial layer
* Though uniform initially, it develops differently in the different RC sections
* This layer will eventually form nearly all of the cellular elements of the CNS
* Except for microglia which come from the reticuloendothelial system
27
What pattern of movement do the dividing cells within the neuroepithelial layer have?
* They oscillated between inner and outer walls
* The process of mitosis happens when they are near the inner wall
* They move back to the outer wall to start going through S phase
* The result is thickening of the walls of the neural tube and enlargements of vesicles at the anterior end
* Some will become neurons, others glial cells
28
In the neuroepithelial layer, what keeps the cells within the inner and outer walls?
* Cell bodies shift along their processes
* There are cell processess attached to the inner and outer walls and the cell bodies move out or in depending on what phase in the cell cycle they are
* Daughter cells can make their own processes OR they can lose them and end up being primed for migration
29
What's up with the radial glial guide cells?
* As the walls of the neural tube are rapidly thickening, cells are moving between the inner and outer walls a lot
* Some of the glial cells form a rope ladder configuration along which primitive nerve cells can migrate
* Becomes necessary as the migration distance gets longer and longer
30
Where in the rapidly thickening walls of the neural tube is the growth the largest and the distance travelled the greatest?
* The telencephalon, which is becoming the cortex where most of the higher level of mental activity occurs
* It is made up of 6 cell layers and each layer is distinct in pattern of organization and connections
* Initially the cells migrate in and form the deepest, or 6th layer
* Each progressive migration forms a more superficial layer
* Think of an inside out sequence of devleopment where each new layer has to move through the deeper one
31
How is the "inside-out" migration scheme responsible for the different architecture of white vs. grey matter in the cortex vs. spinal cord?
* Unlike the spinal cord, where cells proliferate around the ventricular zone then send their axons out toards the periphery (grey matter centrally, white matter outward)
* The cells of the cortex migrate outwards, become established then send their axons and meyelin IN, forming a shell of grey matter and tracts of white matter diving deeper
32
Instead of the RC axis being super important, what axis seems to decide the fate of spinal cord neurons?
* The DV axis
* Those progentior cells closer to ventral aspect will become motor neurons
* Some of these will connect with the myotomes (thus innervate muscles)
* The progenitor cells in the dorsal regions will be sensory, receiving inputs from cells of the DRG (which themselves come from the neural crest)
33
What is the sulcus limitans?
* A crease in the neural tube in the developing spinal cord area
* Separates the ventral from dorsal population of neural progenitor cells
* Ventral - basal plate
* Dorsal - alar plate
34
What are the basal and alar plates?
* A crease in the neural tube in the developing spinal cord area
* Separates the ventral from dorsal population of neural progenitor cells
* Ventral - basal plate
* Dorsal - alar plate
35
What are the most important morphogens involved in dorsoventral patterning?
* Shh = sonic hedgehog (initially secreted by the notochord)
| * BMPs - secreted by lateral ectoderm
36
What's up with BMP signaling in the context of dorsoventral patterning?
* Initially BMP permeate the entire flat embryonic disc
* Secretion of BMP inhibitors by midline primitive node and notochord give rise to a BMP poor medial zone
* Thus pushing cells to commit to midline structures including the neural plate
* BMP rich lateral aspects make up the dorsal arch as the neural tube folds and zippers
* Shh and BMP spatial differences help establish dorsoventral axis
37
How is the cortex given its dorsoventral axis?
* Before the telencephalic vesicles begin to form, the rostral neural tube develops regionally restricted DV markers
* This creates three discrete proliferative zones
* Cortex - most dorsal
* Lateral and medial ganglionic eminences (in the middle)
* Basal forebrain - most ventral
38
What is the result of the telencephalic vesicle folding over itself?
• Formation of the sylvian fissure (lateral sulcus)
• Also buries a patch of cortex within the fissure producing the insular cortex
• The lateral ventricle associated with the telencephalic vesicle is distored into a C shape
• The caudate nucleus is also distorted into a C shape
○ Portion of the gray matter derived from the lateral ganglionic eminence
• The telencephalon structures follow the C shape, and coronal planes will cut through these structures twice
39
What are the putamen and globus pallidus?
* Separated structures by axons emanating from neurons in the cortex which are descending to multiple targets
* They are components of the basal ganglia
* The caudate nucleus is the medial basal ganglia structure
* These are from the telecephalon
40
The third ventricle comes from what?
• Diencephalic vesicle (lumen)
41
In what form does the nervous system begin?
* Flat epithelium called the neurectoderm
* This will round up and form the neural tube
* Formation of the neural tube marks the beginning of neurogenesis
42
When the ventricular walls are being developed (neurogenesis) where are the cell bodies of the precursor cells when they are in S phase?
* Most superficial, or furthest from the inner ventricular wall
* Cell division happens when the cell body is closest to the ventricle, or the inner wall
43
What are the regions in which proliferating cells are found? (neurogenesis)
* Ventricular zones that are the layer closes to the neural tube lumen/ventricle
* Or central canal in the case of the spinal cord
* Dividing cells have processes that attach medially to the ventriclular surface and laterally to the external surface (processes connecting them to the walls of the ventricle)
44
What is the method most used to study neurogenesis?
* Labeling dividing cells with detectable DNA precursors
* H3-thymidine or bromodeoxyuridine
* Cells take up labeled DNA building blocks during S phase
* A cell's birthdate is defined as the time it undergoes its last round of DNA synthesis (S phase)
45
Once a progenitor cell divides close to the ventricular surface, what choice does it have to make?
* It can re-establish it's connection to the outer ventricular wall or it can lose it's inner wall connection
* Re-establishment means it goes through another round of moving and then dividing
* Losing the connections makes it a post-mitotic neuron with it's birthdate the last S phase it went through
46
Describe the progenitor cells that are going through M phase in early neurogenesis
* One of their processes has detached from the external wall of the ventricle (the most superficial wall)
* It maintains it's connection to the inner wall
* The cell body is very close to the ventricular surface (inner wall)
47
When, relative to birth, does neurogenesis occur?
* MOST regions have the majority of neurogenesis occur prior to birth
* Cerebellum is postnatal (granule neurons)
* Many olfactory and hippocampal neurons are postnattaly developed as well
48
What are secondary zones of neurogenesis?
* Hot spots of postnatal neurogenesis
* Cerebellum - external granule layer
* Start out in a layer around the 4th ventricle (ventricular zone)
* They migrate over the purkinje cells and form the neurogenic region (external granule layer, an example of a secondary zone of neurogenesis)
* When they exit the cell cycle they migrate into the cerebellum
* Happens until year 2 postnatal
49
What is the secondary zone of neurogenesis for olfactory neurons?
* The subventricular zone
* Original precursor cells are here, but they migrate to another place to begin dividing prior to exiting the mitotic cycle
* For olfactory, the cells start out right next to the lateral wall of the lateral ventricles
* Migrate not very far laterally to begin division
* Post-mitotic cells migrate anteriorly and rostrally to form olfactory bulb
50
What characteristics do secondary zones of neurogenesis share?
* Arise in ventricular zone
* Migrate before exiting mitotic cyle to a new non-ventricular location
* Proliferate postnatally in non-ventricular zone locations and then often have a little post-mitotic migration as well
51
What are the 3 secondary zones of neurogenesis that were covered?
* External granule layer
* Subventricular zone
* Dentate gyrus
52
Where do hippocampal precursors start out and migrate to?
* Progenitors are in the ventricular zone
| * Migrate to developing dentate gyrus and form their proliferation center
53
What phenomenon seems to determine if a dividing precursor will keep its appendages and keep dividing or stop and migrate?
• The plane of cleavage
• Perpendicular to ventricular surface = keep attachments and majority of daughter cells stay in division cycle
• Parallel to ventricular surface = lose attachments and migrate
○ One of the daughters stays bu the other does not
○ Asymmetrical division
54
What do the genes prospero, numb and miranda have in common?
* Genes that encode asymmetrically localized factors and play a role in cell fate decisions
* Parallel vs. perpendicular planes of cleavage in neurogenesis
55
What is shared unequally between daughter cells that furthers assymmetry?
* Differential inheritance of cytoplasmic proteins, mRNAs and other factors
* Thus in a parallel to the ventricular surface cleavage event one daugher cell keeps its attachments and goes through another round of division while one stops and migrates
* In the dividing cell, the cytoplasm is purposefully organized so that plane of cleavage can decide cell fate
56
What are the zones of migration in the early cerebral cortex?
* Preplate - PP
* MZ - marginal zone
* CP - cortical plate
* IZ - intermediate zone
* SP - subplate
* Deep ventricular zone with proliferating cells
57
What is special about the subplate neurons?
* Play pioneering roles in circuit formation
| * Many will die early once they have played their roles and thus are considered a transient neuronal population
58
What is the preplate?
* PP, about 8-9 weeks embryogenesis
* First neurons to become postmitotic migrate a distance of several cell bodies and form this new region called the preplate
* Preplate will divide into the zones of cerebral cortex formation
59
What cells act as guides for migrating neuron precursors after the preplate is formed?
• Radial glia - specialized glia that keep their processes and act like a rope ladder
60
What are the 3 distinct stages in neuronal migration for the cerebral cortex?
* Onset of migration
* Ongoing migration
* Migration stop
* You can have disorders with each of these processes/steps
61
What is an example of a disease that affects the onset of neuronal migration?
• PH = periventricular heterotopia
• In PH, neurons can't leave ventricular zone so they just differentiate too deep
• PH has an X-linked dominant inheritance
• Males with affected X-chromosome do not typically survive to term
• PH females typically have epilepsy without cognitive abnormalities
*cytoskelatal gene FLNA (filaminA) is mutated
62
What can go wrong in the first step of migration?
* Onset of neuronal migration
* FLNA - filaminA gene mutations can result in PH = periventricular heterotopia
* FLNA - actin-binding crosslinking protein which messes with movement through cytoskelatal problems
* In PH, neurons can't leave ventricular zone so they just differentiate too deep
* PH has an X-linked dominant inheritance
* Males with affected X-chromosome do not typically survive to term
* PH females typically have epilepsy without cognitive abnormalities
63
What are the two proteins implicated in messing up the second stage of migration?
* Second stage = migration process/continuted migration
* DCX = doublecortin - leads to double cortex syndrome
* LIS1 = lissencephaly type one
64
What's up with type I lissencephaly?
* Means smooth brain. Problem with migration
* LIS1 is the protein, on chromosome 17
* Need two healthy copies to be normal. One mutated copy presents with a phenotype
* Leads to a lack of layer specificity. Migrating neurons pop off the "rope ladder" too soon
65
What is the function of the DCX gene?
* Neurons express DCX as they migrate
| * Encodes a protein that colocalizes with microtubules and is thought to be a microtuble organizer
66
What's up with double cortex syndrome?
* DCX is the mutated gene
* Found on X-chromosome
* Affected males resemple the lissencephaly phenotype
* Females with one affected X will have double cortex syndrome
* Epilepsy, mild mental retardation and subcortical band heterotopia
* X-linked inheritance
67
What are the 4 mouse genes that affect the stopping of migration?
* These 4 genes apparently help migrating neurons pop off the radial glia
* Reeler
* Dab1
* Mldlr
* Apoer2
68
What is the human version (disease) of the reeler mouse phenotype?
* LCH - lissencephaly with cerebellar hypoplasia
| * Defect in alternative splicing and a frame shift mutation with truncated protein
69
The products of the Vldlr and Apoer2 genes do what?
* They are reelin receptors, which are on the migrating neurons.
* If they bind reelin that helps them pop off the radial glia
* Apoer2 is cerebral, Vldlr is cerebellar
70
What is Reelin and when is it expressed?
* Large extracellular protein
* Expressed by cells that are transiently present during embryogenesis in the marginal zone and preplate
* Cajal-Retzius cells
* Plays a role in the decision of a cell to stop migrating
71
What does the reeler gene do?
* Reelin protein, mutation result in reversal of inside-out cortical pattern
* Accumulation of neurons in the superficial marginal layer
* Cerebellar problems with mutation - purkinje cells do not form a well-defined layer but distribute in aggregates
* Affects gait
72
What is the general principle of neurogenesis to keep in mind?
* It really matters when an neuron progenitor is born
* Neurons born at the same time tend to end up together in the same layer and follow similar programs of differentiation
73
What is an alternative migration pattern to radial migration?
* Tangential migration
* Results in progeny of a single progenitor being dispersed throughout a particular tissue
* Notable example = inhibitory GABA-containing cells in the cerebral cortex
74
What happens when a developing neuron gets to it's final migratory destination?
* Usually interacts with other neurons to form a distinct nucleus or layer
* Tend to aggregate with other like neurons expressing cell surface markers that are "like" to themselves
* Gradients of surface markers likely are maps that guide CNS development
75
What is the pattern of migration some cells use to get to the olfactory bulb called?
* Rostral migratory stream
| * Chain migration
76
In terms of migration, what is the difference (typically) between pyramidal cells and GABA containing cells?
* Remember pyramidal cells are glutamate-containing cells (excitatory)
* GABA neurons migrate tangentially
* Pyramidal neurons migrate radially
77
Where do GABA containing cells originate?
• Migrate tangentially from portions of the ventricular zone in ventral forebrain gregions known as the lateral and medial ganglionic eminences
78
Where do the neural crest cells originate?
* Arise from the boundary region between the neurectoderm and epidermis
* After neural tube closure, the neural crest is a mass of cells on top of the dorsal tube
79
When neural crest cells are expressing cadherin, what is likely the case?
* They express cadherin when they are done migrating.
| * Thus, these neural crest cells have likely reached their final destination
80
What are the two paths of neural crest migration?
* Dorsal (lateral) stream - pigment cells
* Ventral stream - flows ventromedially and dives under dorsal dermamyotomes and gives rise to sensory, autonomic and enteric ganglia
81
What seems to be the molecular mechanism of guiding neural crest migration?
* Permissive vs. non-permissive surfaces
* Decided by the expression of cell-surface markers and ECM secreted proteins
* Laminin and fibronectin are permissive
* Other cells express surfaces that discourage neural crest migration
82
What structures come from the neural crest cells?
* Peripheral nervous system
* Pigment cells
* Cartilage
* Sensory ganglia
* Enteric nervous system
83
What is the neurotrophic hypothesis
* Deals with apoptosis in neural development
* Targets provide limiting amounts of nutrient or trophic factor that is taken up by input nerve terminals
* Essentially the final destination decides the number and type of neurons it want/needs
84
What are the given examples of neurotrophic factors?
* Promote cell survival
* NGF - nerve growth factor
* BDNF - brain derived neurotrophic factor
* NT-3 (neurotophin-3)
* NT-4/5 (neurotrophin-4/5)
* CNTF - interleukin class with leukemia inhibitor factor (LIF) and cardiotropin
85
What does mutation of BDNF gene result in? (general)
• Hippocampal function and memory formation problems
86
Neurotrophic factors generally do what?
* Inhibit apoptosis
| * As soon as they are not present the cells involved usually die off
87
NGF is important as a trophic factor for what class of neuron?
* Sensory and autonomic neurons, but not CNS
| * CNS neurons don't seem to have a "one major factor" but they instead require multiple concurrent signals for survival
88
What happens intracellularly when a Trk binds a neurotrophin?
* Trk receptors act like other receptors (receptor tyrosine kinase) in that there is dimerization, phosphorylation and recruitment of signaling cascade machinery
* Ras, PI3 kinase and PLC
89
What class of receptors bind neurotrophins?
* Tropomyosin-related kinase family
* Trk's
* Each neurotrophin has a favorite receptor or spread of receptors and vice versa
90
Neurotrophins have what function beyond a survival signal for neurons?
* They play a permissive role in axonal growth
* They induce programs of differentiation that are required for the formation of axons and dendrites
* Add neurotrophins to cultured cells and they form initial processes
* Permissive role, not involved in axonal pathfinding
91
What is up with the oligophrenin-1 protein?
* Modulates the activity of an enzyme that regulates the cytoskeleton
* Can result in mental retardation in mutated
92
What is axonal pathfinding?
* The process of the axon growth cone growing into the environment and ending up connecting to something important
* Membrane, cytoskelatal proteins and other components are needed to sniff out the proper direction
* Growth cone sprouts filopodia which have certain receptor populations that guide further growth
93
What are the long-range guidance molecules?
* Netrins and semaphorins
* Semaphorins can only be repulsive
* Netrins can be repulsive or attractive depending on the rereceptor it binds
94
What are the short-range guidance molecules?
* Cadherins and cell adhesion molecules (CAMs) on the cell surface - attractive
* Collagen, laminin, fibronectin and proteoglycans in the ECM - attractive
* Semaphorins, ephrins (cell surface) - replusion
* Tenascin (ECM) - repulsion
95
What would the binding of a cadherin do?
* Cadherins bind other cadherins
| * Result in calcium dependent adhesion and outgrowth of axon
96
What happens when eph kinases bind their ligand?
* Eph kinases bind ephrins
* Result is chemorepulsion
* Eventually the topgroaphic map is formed by densities of receptor and ligand (visual system)
97
What happens when neuropilins and plexins bind their ligand?
* Neuropilins and plexins bind semaphorins
| * Results in chemorepulsion of axonal growth cone
98
What does the DCC receptor bind?
* Netrins
* Chemoattraction or repulsion
* Midline crossing
* Intracellular cAMP levels will drive the strength of the response
99
When you see alpha4-beta1 receptors, think what?
* Collagens, fibronectin, etc
| * Binding ECM components for local attraction and repulsion of growing axon
100
What would binding of integrins do?
* Integrins are the receptors for ECM moleules
| * Result in local attraction and repulsion
101
Axonal regeneration in the adult CNS deals with what three factors?
* Ability of axons to grow
* Presence of molecules to promote growth
* Presence of molecules and receptors that inhibit growth
102
What is the key experiment described (1996) that used the three principles of axonal regeneration?
* Implantation of a peripheral nerve in an experimentally transected spinal cord
* Regained some function
* Bathed implant in FGF
* Peripheral nerve, so the glia was schwann cell
103
What factors promote axonal regeneration
* NGF - produced by schwann cell
| * FGF = fibroblast growth factor - also promotes axonal growth
104
What might inhibit axonal regeneration in the adult CNS?
* Nogo, epressed by myelin
| * Binds - Nogo66 receptor and seems to be a secreted factor that keeps CNS from regenerating much
105
What function of the neuron seems to play an important role in synapse elimination?
* Electrical activity
* Correlated firing of pre and post-synaptic cells favors selective synapse stabilization
* Asynhronous firing of inputs and target promote synapse elimination
106
The postsynaptic cell plays into synapse stabilization how?
* By secreting a neurotrophin or similar substance
* Pre-synaptic terminals that are retained have somehow preferentially taken up post-synaptically released neurotrophin or neurotrophin-like substance
107
When you see trkB and epilepsy in the same sentence what should you think?
* This is an example of neurotrophins modulating the activity/efficacy of a synapse
* BDNF is the neurotrophin, trkB is the receptor
* Looked at in the treatment of epilepsy
108
In terms of cortical dendritic spines, what is indicative of Down's Syndrome vs. normal?
* Normally, during the first postnatal year the density of cortical dendritic spines increases as dendritic spines thicken
* In DS, dendritic spines are abnormally thin and short
* This may reflect abnormal pruning or synapse maturation
109
When does myelination occur?
* Begins during embryonic stages
* First present in periphery
* CNS, meylination is first observed in the spinal cord near the end of the first trimester
* By third trimester, myelination is in the brain
* Several cortical tracts are myelinated after birth (those in higher level functions)
* Corticospinal tract is myelinated after birth as well
110
How do NT receptors contribute to development?
* In different phases of development GABA receptors are made up of different subunits
* The Ecl changes based on the subunit composition
* There are embryonic forms of the channels and adult forms of the channels
* During developmental stages, intracellular levels of chloride are elevated and thus there is a more depolarized value for Ecl
* Thus GABA can lead to excitation
111
Why does the neonatal brain have a lower seizure threshold?
• GABA receptors can actually lead to EPSPs because of their developmental subunit compostions
112
Dab1 is important for stopping migration how?
* It is an intracellular signalling chain component for the reelin:Apoer2 signaling chain
* Still important for the decision to come off the radial glia
