Whole Module Part 2 Flashcards
(278 cards)
1
Q
Describe the filopodium
A
Polarised F actin able to form larger bundles
2
Q
What is the effect of ablation ectopic studies
A
Neurones are still produced from their domains but fate is altered
3
Q
BDNF is
A
Brain derived growth factor
4
Q
What determine whether a cell crosses the midline
A
Levels of slit at cell surface
5
Q
What layer: Large pyramidal
A
V
6
Q
What drives granule neurone proliferation
A
Shh
7
Q
What is the common origin of the pons and cerebellum
A
Rhombic lip
8
Q
Shh and BMPS specify the
A
Neural fate
9
Q
What is the effect of raising an AB to neural AGRIN
A
Prevents the clustering]
10
Q
What are two causative mutations within the mts
A
TUBA1A TUBB2B
11
Q
How do climbing fibres show an example of synapse refinement
A
In mature cerebellum one climbing fibre : one purkinhe cell … during development can be as many as 4 - location also changes soma –> dendrite
12
Q
Describe pontocerebellar hypoplasia
A
Affects the pons and cerebellum, MATH-1 affected in some forms
13
Q
Describe the connection between cutaneous max and lat dorsi
A
Polysynaptic via interneurone
14
Q
What is the many pheno of reeler mice
A
Ataxia
15
Q
What does AGRIN require
A
Dystroglycan and MuSK
16
Q
Where was NGF purified from
A
Snake venom and mouse sub-maxillary gland
17
Q
What does robo econde
A
Receptor
18
Q
What did the posterior tectal membrane cause to temporal growth cones
A
Collapses
19
Q
What ephrins are expressed in counter gradient in the retina and tectim
A
Ephrin A2 and A5
20
Q
What does TrkA affect
A
Differentiation, growth and movement
21
Q
What is seen in a post crossing axon with an ectopic FP
A
Axon stalls due to inhibitory sema/slit from the ectopic fp
22
Q
Two types of semaphorins
A
Membrane bound or secreted
23
Q
What are some of the NCCs retained as
A
RP cells
24
Q
Temporal axons go
A
Anteiror
25
What is axonotmesis
Axons divided
26
What laminae is proprioception
Laminae III - IV
27
How can cre-recombinase be used to create tissue specific knockouts
Two loxP sites either side of the gene that you want to knockout - express Cre recombinase under the influence of a tissue specific promoter
28
How many layers of the cerebellum
4
29
What determines if an axon will corss the midline
Lelevs of slit at the cell surface
30
Where do sub-plate neurones usually project prior to innervation of cortex by LGN
Cortex--> thalamus
31
Merker cells are what
Specicalised epitherlium which overly the free nerve endings forming merkel discs
32
Explain the robo mutant phenotype
No robo so no detection of slit so neurones go back and forth
33
Epineurium
Surrounds the whole nerve
34
What is one way of treating spinal cord damage
Controlling the inflammatory process
35
What is the only injury where nerve conduction distal to the injury is maintained
Neuropraxia
36
What layer: small pyramidal cells
II
37
NTF3 binds to
TRKC TRK1a1B P75
38
What is the ephrin A2 A5 double knockout phenotype
Temporal neurones project into the posteiror tectum thus distorting the topographic map
39
Where does M phase occr
At the VZ
40
What is cylopamine, what can it be used for
Inhibitor of smo so blocks Shh signalling
41
Different neuronal types exhibit different
Neurotrophic dependency
42
Give an example of a sysytem which has topology
Retino-tectal
43
In vitro what do CNS neurones avoid
Oligodendrocytes
44
Comm mutant
No crossing of the midline
45
What is ARIA a member of
Neuregulin gene (NRG-1 gene)
46
What are CR cells important in
Telling migrating cell when to stop
47
What is the critical period of xenopus tadpole regneration
Either side of this period tail will grow back - but NOT DURING THE CRITICAL PERIOD
48
How many bp is a LOXP site
34
49
What does removal of chick limb bud do
Fewer DRG and motor neurone s
50
Anterior (sup) rhombic lip gives rise to
Ganuel neurone precurrsors
51
Do newly born neurones have any dependent
No - havent sent axons yet so no dependeny
52
What Is expressed to cause cells to take an excitatory NT fate
Gsx1/2
53
What do the subplate and cajal retizus cells form
Preplate (PP)
54
Primary determinat for connection survival is
Coordinated pre and post synaptic electrical activity
55
How many nogos
3
56
What two components occur the allow the filopodium to extend
Actin-myosin based actin tubulin link pulls microtubles into the wake of extending filopodia ---- Two molecular clutch engages to slow rearward actin treadmilling
57
What is the effect of a crush injury
Basal lmaina and ECM likley to still be intact
58
Does lamin have any effect on direction
No just simply allows growth
59
What gene in vert is expressed on in precrossing fibres
Rig1 - Robo3
60
What is the low affinity NGF R
P75-NTR
61
Descirbe how differential gene expresison is seen at the NMJ
Transcription increases in adjacent nuclei but decreases further away
62
What three factors dictate where synapses form
Approaching growth cone talks to target, site availabilities may be restricted, post synaptic cells may have pre-prepared sites
63
Nasal axons go
Posterior
64
What does the corticle plate sit between
Marginal zone and subplate
65
What do ephrins help with early and then later
Compartmentalise the embryo, then used to keep axons out of specific areas and creation of a topological map
66
Describe how receptor clustering occurs at the NMJ
Before growth cone receptors are at what conc 1000 /umsrd but after 10000 /umsqrd
67
Cre recombinase can be used to
Create tissue specific knockouts
68
How does neurotransmitter choice vary
Depends on the environment
69
Roundabout mutant
Constant crossing of the midline
70
Muscle spindles reequire what to differentiate
Require sensory to differentiate
71
What is the common origin of the pons and cerebellum
Rhombic lip
72
What does addition of chick limb bud cause
More DRG and motor neurones
73
Where was agrin purified from
T.California
74
Which direction are neurotrophins synth by the neurone transported
Anteriograde (away from cell body)
75
Production of rhombic lip cells is controlled by what transcription factor
MATH-1
76
What organisms are neurotrophins not found in
Drosophila and C.elegans
77
NOGO A
200 kd - found in oligodendrocytes and developing neruones
78
Descrie the effect of knocking out agrin
Deffective neuromuscular junction
79
What occurs following autoimmunisation to myelin proteins
Increased regeneration
80
Describe how it can be seen that the BL induces receptor clustering
When muscle cell MNs removed cell can grow, this causes the re-clustering of the receptors so this is highly important in regeneration
81
Whar are the alpha and gamma subunits important for
Alpha and gamma
82
What is neurotmesis on the sunderland scale
5
83
Two examples of radial migration
Inkenetic nuclear migrations in the neuroeptithellum and to establish layered structu (e.g. cerebellum)
84
What are heterochronic transplants used for
To test plasticity of neurones
85
What is the cereblellum output
Via purkinje cells
86
How do axons control when to get off/stay on scafoold
By controlling fasiculuation
87
Cells expressing BMP7 can
Mimic the action of the roof plate
88
What is the cell adhesion molecule in insects
Fas2
89
Cerebellum is derived from
Neural crest cells
90
Subunits of NGF
2 alpha 1 beta 2 gamma
91
What happens if comm expression is forced
Gives the same phenotype as robo - robo expression is lost everywhere
92
Where are the two major zones of neural stem cells
Dentat gyrus of hippocampus, SVZ of 4th ventricle
93
Perineurium
Surrounds one fasicle
94
BDNF binds to
TRKB P75
95
Desribe the path of sensory relay neurones
From RP to FP
96
NOGO C
25 Kda - muscle cells
97
Four forces of axon guidance
Contact attraction, chemoattraction, contact repulsion, chemorepulsion
98
Posterior (inf) rhombic lip gives rise to
Pontine nuclei and the inferior olive
99
What cab be used to help a sutured nerve grow back
Design of a scaffold to bridge the gap
100
What is the attractive cue expressed by the FP
Netrin
101
Less target means
Fewer synapses and neurones
102
The fact that in a netrin -/- some neurones reach the FP is an example of
Genetic redundancy
103
Precurssor to NGF (pre-NGF) binds to
P75-NTR
104
Loss of Rig1/robo3 gives what phenotype
Failure of the C axons to cross the midline
105
What type of enzyme is TrkA
RTK
106
What does comm encode
Trafficking protein
107
What is AGRIN made by
Motor neurones and myocytes
108
What is neurapraxia
Conduction block - due to loss of conducting tissue
109
NT4/5
TRKB P75
110
What can be concluded from a cut an paste of the floor plate to side of roof plate
Axons attracted to FP so FP must be secreteting an attractive cue
111
What are some morphological synpase development
Small vesicles at pre sy membrane, narrow cleft filled with ECM, post synaptic density (membrane appears thickened)
112
Early precurrsor fate
Plastic - can be changed
113
What type of epithelium is early neuroepithelium
Pseudostratified
114
Merkle cells are present
Before sensory innervation
115
What transcription factor regulates the production of the cells of the rhombic lip
MATH-1
116
Levels of Shh affect what in the cerebellum
Ammount of lobulation
117
Describe how the ANS expt shows example of transmitter choice depends on environment
Transplant symp into para --> NT changes to ACH (vice versa) for other way
118
3 domains of the growth cone
Central trans, and peripheral
119
What are glial scars
Cysts full of the wrong sort of ECM
120
What is significant about the growth of axons in the presence of laminin
Only permissive for growth within certain concentration ranges
121
What happens if part of the subplate ablated before axons extend
LGN innervation fails in the ablated region
122
Describe the location of the cerebellum
Root of the fourth ventricle above the medulla
123
What can be said of the regeneraiton capacity of lower vert
Have increased regen capacity
124
What is the blastema
Bundling of cells which has become pluripotent but with some memory of the tissue of organisation
125
What is a permissive factor
Factors which allow the growth of axons
126
What occurs when Abs raised against NGF
Block DRG growth in vivo
127
What is seen when cyclopanime applied
Fewer commissureal axons reach the floor plate so can be seen that Shh works as chemoattractant
128
What were the results of birthdating cells in the cortex
Neurones of diferent layers were born at different times
129
What are semaphorins
Family of inhibitory guidance cues
130
What is seen in Ti1-->Cx1 growth when sema 1 knocked out
The axons is able to stray into wrong areas of the limb
131
Ephrin receptors are
Ephs
132
At the hindbrain:midbrain boundary what do cells of the roof plate form
The roof plate cells retain huge proliferative potential forming cells of the rhombic lip - these go on to form many neurones of the cerebellum
133
Xenopus tadpole regner triggered by
BMPs
134
Ectopic exp of netrin (target selection)
Forced in wrong muscle ==> wrong connection
135
Cre remcombinase cleaves at
LoxP sites
136
Way in which we go to circuits
Tfs define the phenotype - this NT phenotype defines function - Neurones send axons to other axons - Connections will be est and refine by activity based pruning
137
What are one of the most proliferative cell types
External granular layer cells
138
CEREBELLUM: What would be seen if Shh was mutatetd
Meddulloblastoma
139
Explain bypass phenotype
Novel/overfasciculation all axons miss targets
140
Loss of nectrin (target slection)
Like ablating targets - synapses not made despite targets being there
141
What does BMP7 cause
Causes commissural axon growth cone collapse
142
What is the effect of raising an AB to muscle AGRIn
No effect
143
NOGO B
55 Kda - many cell types
144
What is one mechanism for silent synpases
Initially NMDA R blocked with MG, high freq stimulation leads to depol of the PM, Mg dragged out of the receptor, Ca leads to upregulation of AMPA R - AMPA R is electrically active
145
What are the mechanism for regeneration
Mitosis of the schwann cells, formation of the bands of bunger, regrowth along the dividing scwhann cells and sprouting
146
What are the first post-mitotic cells to appear
CR cells
147
What is the effect of no MATH1
No foliation, no IGL, no pontine nuclei
148
What gradient caused the results of the stripe assay
Due to ephrin gradient
149
How many layers of the cortex
5
150
What is the Mr of ARIA
42 kd
151
Where are stem cells found in mammals
Forebrain SVZ and dentate gyrus
152
What is lamin
Growth promoting ECM molecules - localised to optic nerve
153
What is neurotmesis
Nerve becomes divided
154
What is the post mitotic mechanism of neuronal diversity generation
Specification --> maturation --> NT expression --> NT recptor expression
155
What changes occur when a growth cone turns into a presynapse
Filopodia retract and tight junction forms, memrbane and EC glycoproteins added, pre sy vesicles, dense ECM and receptors accumulate in the cleft
156
Spinal cord injuries can lead to
Loss of muscle tone and other injuries
157
Descitibe the lamella
F actin is bundled into a net
158
If NGF present in central compartment only
Surivival of the cell bodies, axons die and retract
159
Ectopic exp of Fas2
Innervation of new targets
160
What does growth cone collapse cause
Destabilisation of the F-actin
161
What is regeneration of a strucutre dependent on
Presence of a nerve
162
What happens to subplate neurones, what are they required for
eventually die but imp for guiding thalamic axons
163
Mixture of neurones fasciulate wit
Their own kind
164
Effect of ACHR alon
No clustering
165
What do anterior rhombic lip cells form
Granule neurone precurrsors
166
Descirbe how the NMJ changes with time
Early is multiply innervated - refined to a single innervation
167
Axons can reprogram at intermediate targets, give an example
Eg when an axons has crossed the midline it is no longer attract to the floor plate
168
What happens for Ti1 --> Cx1 if last signpost ablated
Growth cone stalls and doesn’t make the last medial tuns
169
What transcription factor is important in the setting up of inhibitory neuropep/transmitter phenotypes
PAX2
170
What is ARIA
Ach receptor inducing activity
171
Synchronous act leads to
Synapse strenghtening
172
How many BP woulld there need to be for a loxP to occur by chance
10^18
173
What does agrin bind to
Muscle specific kinase (MuSK)
174
Shh determines tissue pattern in the cerebellum so a mutation in Shh would cause
Medulloblastoma
175
Cell death is more likely to occur
Closer to the soma
176
Where is Fas2 normally exp
On target and motor axon
177
What occurs to C axons after crossing the FP
Become sensitive to repellents such as semaphorins and slit proteins
178
What are the two forms of agrin
Neural and muscle
179
Describe the effect of comm on robo
Comm prevents robo reaching cell surface so without any robo no sensitivity to slit so able to cross midline
180
What are ephrins
Non permissive contact repellant factors
181
What did the stripe assay show
Cells of the posterior tectum made a non permisisve factor which repels axons of the temporal retina
182
What is one of the main outputs of the cerebllum
Via the purinje cells
183
Shh stimulates mitosis of th cells in the EGL, where is it released from
Purkinje layer
184
What can non permissive factors be used for
Channelling of axon growth ie in Ti1 --> Cx1
185
What is the dependent of trigeminal neurones
BDNF and NTF early - then NGF - then NGF or MSP
186
Describe the treadmilling of F-actin when an attractive cue is encountered
Treadmilling of F-actin and F-actin accumulates
187
What is a method of birth dating cells
Inject titrated thymidine, incorp into cells during S phase, cells in their final division retain the label
188
Four methods of spinal cord repair
Transplant foetal cells, transplant H-ESC derived progenitors, transplant umbilical cells, transplant autologous NS cells or other cells
189
What two possibilites for topogrpahic mapping prop by Sperry
Each axon has unique lable with comp lable on target // coordinate grid of gdts of signals and receptors
190
What occurs when anti nogo used
Improvs regeneration in the spinal cord, results in K/O nogo were variable
191
What are some neural crest retained as
Roof plate cells
192
How does activity of a synapse affect neurotrophin take up
More active - more neurtrophin taken up by membrane recyling
193
Contact between two neurones of different timp leads to
Collapse of the growth cone
194
How are lipophilic dyes used
Have lipophilic domains so adsorbed onto the membrane of cells and flows down the whole membrane
195
How is loss an example of synapse refinement
Loss of motor neurones through competitions - from multiple innervations to single innervations
196
What does arrival at the target often coinside with
New expression of neurotrophin by the target
197
Describe the connection between Mns ans pecs and tricpes
Monosynaptic
198
Effect of AChR and Rapsyn
Clusters
199
What is seen in males
Many SNB motor neuroens
200
What occurs when growth cone restin, how does this change when growth cone encounters an attractive cue
Resting --> Tubulin dragged sporadically into the filopodia - this dragging occurs more frequently when growth cone encounters and attracte cue
201
Where is comm usually only expressed
In neurones which normally corss the midline
202
What is a causative mutation that affects MAP
LISI DCX
203
What is neurapraxia on the sunderland scale
1
204
Where are the cells of the cerebellum formed
Born in ventricular zone
205
What is the location of the largest numebr of neurones in the CNS
Cerebellum
206
What can be said of the expression of ephs and ephrins
Have reciprocal expression in the mmamlian embryo
207
What encodoes cre recombinase
Bacteirophage P1
208
Describe pontocerebellar hypoplasia
Affects the pons and cerebellum, MATH-1 is affected in some forms this reflects the common origin (rhombic lip) of the pons and cerebellum
209
What is the effect of a cut injury
Basal lamina and ECM disrupted
210
What does the accumulation of F actin cause
Stab of the filopodia dragging microtubules into the back of the filopodium
211
What is seen before corssing with an ectopic floor plate
C axon is attracted (normal response to netrins_
212
What type of binding molecules is Fas2
Homophilic binding by cell adhesion molecules
213
What is one of the main roles of the cerebellum
Motor learning
214
What affects motor neurone pooling accounting for sex differences
Testosterone
215
Where are the neurones of the cerebellum bord
Ventricular zone
216
Three nerves of the trigeminal nucelus
Opthalamic nerve, mandibular nerve, maxillart nerve
217
What does circuit completion require
Feedback from the target
218
Key points of synapses formation
Competivie
219
What are the effects of muscle denervation
Muscle atrophy - dedif of the muscle (exp of embryonic mAchR and increased levels of MuSK) external electrical input is able to - help prevent atrophy
220
Where are cajal retzius cells
Marginal layer (subplate neurones below)
221
LAMIN IS ______ BUT NOT ______
Permissive but not instructive
222
Why are there some objections to NOGo
No correlation between NOGO receptor level and regen, much myelin removed by macrophages after damage, regeneration poor in the grey matter too
223
What is the affect of Rig1/robo3
Blocks robo1
224
What layer of the cortex is the oldest
1
225
What is expressed to cause cells to take an inhib NT fate
PTF1A
226
Effect of ectopic expression of Fas2
Cells that do not normally adhere, adhere and aggregate
227
Shh released from the purkinje layers stimulates
Mitosis in the EGL
228
What is the vert homologue of robo , where and when is it expressed
on C axons, before AND after crossing
229
Sema 2 is
Secreted
230
What stimulates mitosis of cells in the external granular layer
Shh
231
What is the result of a loss of Pea3
Results in the MNs motor neurones innervating the CM and LD that have the morphology of the triceps and pect innervating MNs and abberant proprioceptive connections
232
Do growth cones turn>
No they reoragnaise
233
What is the active component of NGF
beta s/u
234
Sema 1 is
Cell surface
235
What occurs when there is no MATH-1
No foliation, no IGL and no pontine nuceli
236
NGF binds to
TRKA and P75
237
Where do inhibitory interneurones of the cortex migrate in from
Subpallium
238
How does NMJ innervation change over time
Initially mutliple motor neurones innervating but reduced by competion until it is just a single fibre innervating one muscle cell
239
Nerve cord in flies lies
Ventrally
240
Extra target
More synapses and neurones
241
Effect of rapsyn only
Clusters
242
What are the layers of the cerebellum
Ext gran layer, molecular layer, purkinje layer, internal granular layer
243
Target derived factors are important for
Formation of reflexes
244
Late precurrsor fate
Fixed - adopts the fate of the host
245
Describe the location of the cerebellum
Root of the fourth ventricle above the medulla
246
What is the high affinity NGF R
TrkA
247
What is seen in Ti1->CX1 growth when sema 2 is blocked
There is no final turn of the axon into the body so sema 2 gdt directs the axons toward the body
248
What laminae is touch
II (inner) to V
249
How many layers of the cerebellum
4
250
What is the function of olfactor ensheathing cells
Wrap olfactor axon bundles
251
Effect of a rapsyn k/o
No clusters
252
If NGF present in all of the chambers
Cells OK
253
What layer: Stellate cells
IV
254
What laminae is pain (thermo)
I and II
255
What is the effect of ARIA
Increase in the synthesis of AChR subunit mRNA - especially the epsilon subunit (in the immature form)
256
What occurs with spinal chord injuries
Sprouting occurs following by failed regen and degen, formation of cysts and glial scards,
257
Where is the largest number of neurones in the CNS
Cerebllum
258
Endoneurium
Around indiviudal axons within fasciles
259
What is the effect of enhanced of WNT signalling
Dorsal gene expression domain is expanded ventrally
260
What occurs for Ti1 --> Cx1 in mice lacking Sema3A
Axons able to stray into wrong territories
261
What induces receptor clustering
Basal lamina
262
What can be said of the recovery of connections in the spinal cord
Very poor
263
Describe nectin
Associated with ECM - like laminin, cells expressing the netrin gene can mimic the attractive nature of the floor plate
264
smooth brain - misencephaly
Loss of gyri and sulci
265
Fish and salamander lack
NOGO A
266
Incidence of medulloblastoma
500 births/year
267
For synapse formation we require
Correct receptors, location, part of membrane to be synapse, receptors must match target tissue, correct number of synpases must be mad e
268
How does blocking of activity lead to a change in survival
Prevents the initiation of cell death mechanisms ==> no competition, fewer losses so more neurones survive
269
When does synapse desity increase in the cat visual cortex
Around post natal day 10 - with the eyes open
270
What do posterior rhombic lip cells form
Pontine nuclei and inferior olive
271
What is the main attractive cue from the Fp
Netrins
272
Descirbe the hebbian synapse
Coordinated activity of a pre and post synaptic terminal strengthens the connection between them
273
Describe the labelled pathway hypothesis
Axons selectively fasicualte with others due to the srufaces carrying cues. Different growth cones express different receptor sets for these cues. Early pioneer axons form a scaffold
274
What neurones found in the trigeminal nucelus
DiLA/DBLa neurones
275
What injury is likley to regrow bettwe with more accuratly
Crush
276
What is the effect of reduced WNT signalling
Ventral genes are expressed more dorsally
277
What are crucial for migration
Microtubules
278
What is the migraiton of newly born neuronal precurrsors
Lateral migration from VZ to the mantle zone where they diff
