Whole Module Part 2 Flashcards
Describe the filopodium
Polarised F actin able to form larger bundles
What is the effect of ablation ectopic studies
Neurones are still produced from their domains but fate is altered
BDNF is
Brain derived growth factor
What determine whether a cell crosses the midline
Levels of slit at cell surface
What layer: Large pyramidal
V
What drives granule neurone proliferation
Shh
What is the common origin of the pons and cerebellum
Rhombic lip
Shh and BMPS specify the
Neural fate
What is the effect of raising an AB to neural AGRIN
Prevents the clustering]
What are two causative mutations within the mts
TUBA1A TUBB2B
How do climbing fibres show an example of synapse refinement
In mature cerebellum one climbing fibre : one purkinhe cell … during development can be as many as 4 - location also changes soma –> dendrite
Describe pontocerebellar hypoplasia
Affects the pons and cerebellum, MATH-1 affected in some forms
Describe the connection between cutaneous max and lat dorsi
Polysynaptic via interneurone
What is the many pheno of reeler mice
Ataxia
What does AGRIN require
Dystroglycan and MuSK
Where was NGF purified from
Snake venom and mouse sub-maxillary gland
What does robo econde
Receptor
What did the posterior tectal membrane cause to temporal growth cones
Collapses
What ephrins are expressed in counter gradient in the retina and tectim
Ephrin A2 and A5
What does TrkA affect
Differentiation, growth and movement
What is seen in a post crossing axon with an ectopic FP
Axon stalls due to inhibitory sema/slit from the ectopic fp
Two types of semaphorins
Membrane bound or secreted
What are some of the NCCs retained as
RP cells
Temporal axons go
Anteiror
What is axonotmesis
Axons divided
What laminae is proprioception
Laminae III - IV
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
How many layers of the cerebellum
4
What determines if an axon will corss the midline
Lelevs of slit at the cell surface
Where do sub-plate neurones usually project prior to innervation of cortex by LGN
Cortex–> thalamus
Merker cells are what
Specicalised epitherlium which overly the free nerve endings forming merkel discs
Explain the robo mutant phenotype
No robo so no detection of slit so neurones go back and forth
Epineurium
Surrounds the whole nerve
What is one way of treating spinal cord damage
Controlling the inflammatory process
What is the only injury where nerve conduction distal to the injury is maintained
Neuropraxia
What layer: small pyramidal cells
II
NTF3 binds to
TRKC TRK1a1B P75
What is the ephrin A2 A5 double knockout phenotype
Temporal neurones project into the posteiror tectum thus distorting the topographic map
Where does M phase occr
At the VZ
What is cylopamine, what can it be used for
Inhibitor of smo so blocks Shh signalling
Different neuronal types exhibit different
Neurotrophic dependency
Give an example of a sysytem which has topology
Retino-tectal
In vitro what do CNS neurones avoid
Oligodendrocytes
Comm mutant
No crossing of the midline
What is ARIA a member of
Neuregulin gene (NRG-1 gene)
What are CR cells important in
Telling migrating cell when to stop
What is the critical period of xenopus tadpole regneration
Either side of this period tail will grow back - but NOT DURING THE CRITICAL PERIOD
How many bp is a LOXP site
34
What does removal of chick limb bud do
Fewer DRG and motor neurone s
Anterior (sup) rhombic lip gives rise to
Ganuel neurone precurrsors
Do newly born neurones have any dependent
No - havent sent axons yet so no dependeny
What Is expressed to cause cells to take an excitatory NT fate
Gsx1/2
What do the subplate and cajal retizus cells form
Preplate (PP)
Primary determinat for connection survival is
Coordinated pre and post synaptic electrical activity
How many nogos
3
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
What is the effect of a crush injury
Basal lmaina and ECM likley to still be intact
Does lamin have any effect on direction
No just simply allows growth
What gene in vert is expressed on in precrossing fibres
Rig1 - Robo3
What is the low affinity NGF R
P75-NTR
Descirbe how differential gene expresison is seen at the NMJ
Transcription increases in adjacent nuclei but decreases further away
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
Nasal axons go
Posterior
What does the corticle plate sit between
Marginal zone and subplate
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
Describe how receptor clustering occurs at the NMJ
Before growth cone receptors are at what conc 1000 /umsrd but after 10000 /umsqrd
Cre recombinase can be used to
Create tissue specific knockouts
How does neurotransmitter choice vary
Depends on the environment
Roundabout mutant
Constant crossing of the midline
Muscle spindles reequire what to differentiate
Require sensory to differentiate
What is the common origin of the pons and cerebellum
Rhombic lip
What does addition of chick limb bud cause
More DRG and motor neurones
Where was agrin purified from
T.California
Which direction are neurotrophins synth by the neurone transported
Anteriograde (away from cell body)
Production of rhombic lip cells is controlled by what transcription factor
MATH-1
What organisms are neurotrophins not found in
Drosophila and C.elegans
NOGO A
200 kd - found in oligodendrocytes and developing neruones
Descrie the effect of knocking out agrin
Deffective neuromuscular junction
What occurs following autoimmunisation to myelin proteins
Increased regeneration
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
Whar are the alpha and gamma subunits important for
Alpha and gamma
What is neurotmesis on the sunderland scale
5
Two examples of radial migration
Inkenetic nuclear migrations in the neuroeptithellum and to establish layered structu (e.g. cerebellum)
What are heterochronic transplants used for
To test plasticity of neurones
What is the cereblellum output
Via purkinje cells
How do axons control when to get off/stay on scafoold
By controlling fasiculuation
Cells expressing BMP7 can
Mimic the action of the roof plate
What is the cell adhesion molecule in insects
Fas2
Cerebellum is derived from
Neural crest cells
Subunits of NGF
2 alpha 1 beta 2 gamma
What happens if comm expression is forced
Gives the same phenotype as robo - robo expression is lost everywhere
Where are the two major zones of neural stem cells
Dentat gyrus of hippocampus, SVZ of 4th ventricle
Perineurium
Surrounds one fasicle
BDNF binds to
TRKB P75
Desribe the path of sensory relay neurones
From RP to FP
NOGO C
25 Kda - muscle cells
Four forces of axon guidance
Contact attraction, chemoattraction, contact repulsion, chemorepulsion
Posterior (inf) rhombic lip gives rise to
Pontine nuclei and the inferior olive
What cab be used to help a sutured nerve grow back
Design of a scaffold to bridge the gap
What is the attractive cue expressed by the FP
Netrin
Less target means
Fewer synapses and neurones
The fact that in a netrin -/- some neurones reach the FP is an example of
Genetic redundancy
Precurssor to NGF (pre-NGF) binds to
P75-NTR
Loss of Rig1/robo3 gives what phenotype
Failure of the C axons to cross the midline
What type of enzyme is TrkA
RTK
What does comm encode
Trafficking protein
What is AGRIN made by
Motor neurones and myocytes
What is neurapraxia
Conduction block - due to loss of conducting tissue
NT4/5
TRKB P75
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
What are some morphological synpase development
Small vesicles at pre sy membrane, narrow cleft filled with ECM, post synaptic density (membrane appears thickened)
Early precurrsor fate
Plastic - can be changed
What type of epithelium is early neuroepithelium
Pseudostratified
Merkle cells are present
Before sensory innervation
What transcription factor regulates the production of the cells of the rhombic lip
MATH-1
Levels of Shh affect what in the cerebellum
Ammount of lobulation
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
3 domains of the growth cone
Central trans, and peripheral
What are glial scars
Cysts full of the wrong sort of ECM
What is significant about the growth of axons in the presence of laminin
Only permissive for growth within certain concentration ranges
What happens if part of the subplate ablated before axons extend
LGN innervation fails in the ablated region
Describe the location of the cerebellum
Root of the fourth ventricle above the medulla
What can be said of the regeneraiton capacity of lower vert
Have increased regen capacity
What is the blastema
Bundling of cells which has become pluripotent but with some memory of the tissue of organisation
What is a permissive factor
Factors which allow the growth of axons
What occurs when Abs raised against NGF
Block DRG growth in vivo
What is seen when cyclopanime applied
Fewer commissureal axons reach the floor plate so can be seen that Shh works as chemoattractant
What were the results of birthdating cells in the cortex
Neurones of diferent layers were born at different times
What are semaphorins
Family of inhibitory guidance cues
What is seen in Ti1–>Cx1 growth when sema 1 knocked out
The axons is able to stray into wrong areas of the limb
Ephrin receptors are
Ephs
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
Xenopus tadpole regner triggered by
BMPs
Ectopic exp of netrin (target selection)
Forced in wrong muscle ==> wrong connection
Cre remcombinase cleaves at
LoxP sites
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
What are one of the most proliferative cell types
External granular layer cells
CEREBELLUM: What would be seen if Shh was mutatetd
Meddulloblastoma
Explain bypass phenotype
Novel/overfasciculation all axons miss targets
Loss of nectrin (target slection)
Like ablating targets - synapses not made despite targets being there
What does BMP7 cause
Causes commissural axon growth cone collapse
What is the effect of raising an AB to muscle AGRIn
No effect
NOGO B
55 Kda - many cell types
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
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
What are the first post-mitotic cells to appear
CR cells
What is the effect of no MATH1
No foliation, no IGL, no pontine nuclei
What gradient caused the results of the stripe assay
Due to ephrin gradient
How many layers of the cortex
5
What is the Mr of ARIA
42 kd
Where are stem cells found in mammals
Forebrain SVZ and dentate gyrus
What is lamin
Growth promoting ECM molecules - localised to optic nerve
What is neurotmesis
Nerve becomes divided
What is the post mitotic mechanism of neuronal diversity generation
Specification –> maturation –> NT expression –> NT recptor expression
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
Spinal cord injuries can lead to
Loss of muscle tone and other injuries
Descitibe the lamella
F actin is bundled into a net
If NGF present in central compartment only
Surivival of the cell bodies, axons die and retract
Ectopic exp of Fas2
Innervation of new targets
What does growth cone collapse cause
Destabilisation of the F-actin
What is regeneration of a strucutre dependent on
Presence of a nerve
What happens to subplate neurones, what are they required for
eventually die but imp for guiding thalamic axons
Mixture of neurones fasciulate wit
Their own kind
Effect of ACHR alon
No clustering
What do anterior rhombic lip cells form
Granule neurone precurrsors
Descirbe how the NMJ changes with time
Early is multiply innervated - refined to a single innervation
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
What happens for Ti1 –> Cx1 if last signpost ablated
Growth cone stalls and doesn’t make the last medial tuns
What transcription factor is important in the setting up of inhibitory neuropep/transmitter phenotypes
PAX2
What is ARIA
Ach receptor inducing activity
Synchronous act leads to
Synapse strenghtening
How many BP woulld there need to be for a loxP to occur by chance
10^18
What does agrin bind to
Muscle specific kinase (MuSK)
Shh determines tissue pattern in the cerebellum so a mutation in Shh would cause
Medulloblastoma
Cell death is more likely to occur
Closer to the soma
Where is Fas2 normally exp
On target and motor axon
What occurs to C axons after crossing the FP
Become sensitive to repellents such as semaphorins and slit proteins
What are the two forms of agrin
Neural and muscle
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
What are ephrins
Non permissive contact repellant factors
What did the stripe assay show
Cells of the posterior tectum made a non permisisve factor which repels axons of the temporal retina
What is one of the main outputs of the cerebllum
Via the purinje cells
Shh stimulates mitosis of th cells in the EGL, where is it released from
Purkinje layer
What can non permissive factors be used for
Channelling of axon growth ie in Ti1 –> Cx1
What is the dependent of trigeminal neurones
BDNF and NTF early - then NGF - then NGF or MSP
Describe the treadmilling of F-actin when an attractive cue is encountered
Treadmilling of F-actin and F-actin accumulates
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
Four methods of spinal cord repair
Transplant foetal cells, transplant H-ESC derived progenitors, transplant umbilical cells, transplant autologous NS cells or other cells
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
What occurs when anti nogo used
Improvs regeneration in the spinal cord, results in K/O nogo were variable
What are some neural crest retained as
Roof plate cells
How does activity of a synapse affect neurotrophin take up
More active - more neurtrophin taken up by membrane recyling
Contact between two neurones of different timp leads to
Collapse of the growth cone
How are lipophilic dyes used
Have lipophilic domains so adsorbed onto the membrane of cells and flows down the whole membrane
How is loss an example of synapse refinement
Loss of motor neurones through competitions - from multiple innervations to single innervations
What does arrival at the target often coinside with
New expression of neurotrophin by the target
Describe the connection between Mns ans pecs and tricpes
Monosynaptic
Effect of AChR and Rapsyn
Clusters
What is seen in males
Many SNB motor neuroens
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
Where is comm usually only expressed
In neurones which normally corss the midline
What is a causative mutation that affects MAP
LISI DCX
What is neurapraxia on the sunderland scale
1
Where are the cells of the cerebellum formed
Born in ventricular zone
What is the location of the largest numebr of neurones in the CNS
Cerebellum
What can be said of the expression of ephs and ephrins
Have reciprocal expression in the mmamlian embryo
What encodoes cre recombinase
Bacteirophage P1
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
What is the effect of a cut injury
Basal lamina and ECM disrupted
What does the accumulation of F actin cause
Stab of the filopodia dragging microtubules into the back of the filopodium
What is seen before corssing with an ectopic floor plate
C axon is attracted (normal response to netrins_
What type of binding molecules is Fas2
Homophilic binding by cell adhesion molecules
What is one of the main roles of the cerebellum
Motor learning
What affects motor neurone pooling accounting for sex differences
Testosterone
Where are the neurones of the cerebellum bord
Ventricular zone
Three nerves of the trigeminal nucelus
Opthalamic nerve, mandibular nerve, maxillart nerve
What does circuit completion require
Feedback from the target
Key points of synapses formation
Competivie
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
Where are cajal retzius cells
Marginal layer (subplate neurones below)
LAMIN IS ______ BUT NOT ______
Permissive but not instructive
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
What is the affect of Rig1/robo3
Blocks robo1
What layer of the cortex is the oldest
1
What is expressed to cause cells to take an inhib NT fate
PTF1A
Effect of ectopic expression of Fas2
Cells that do not normally adhere, adhere and aggregate
Shh released from the purkinje layers stimulates
Mitosis in the EGL
What is the vert homologue of robo , where and when is it expressed
on C axons, before AND after crossing
Sema 2 is
Secreted
What stimulates mitosis of cells in the external granular layer
Shh
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
Do growth cones turn>
No they reoragnaise
What is the active component of NGF
beta s/u
Sema 1 is
Cell surface
What occurs when there is no MATH-1
No foliation, no IGL and no pontine nuceli
NGF binds to
TRKA and P75
Where do inhibitory interneurones of the cortex migrate in from
Subpallium
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
Nerve cord in flies lies
Ventrally
Extra target
More synapses and neurones
Effect of rapsyn only
Clusters
What are the layers of the cerebellum
Ext gran layer, molecular layer, purkinje layer, internal granular layer
Target derived factors are important for
Formation of reflexes
Late precurrsor fate
Fixed - adopts the fate of the host
Describe the location of the cerebellum
Root of the fourth ventricle above the medulla
What is the high affinity NGF R
TrkA
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
What laminae is touch
II (inner) to V
How many layers of the cerebellum
4
What is the function of olfactor ensheathing cells
Wrap olfactor axon bundles
Effect of a rapsyn k/o
No clusters
If NGF present in all of the chambers
Cells OK
What layer: Stellate cells
IV
What laminae is pain (thermo)
I and II
What is the effect of ARIA
Increase in the synthesis of AChR subunit mRNA - especially the epsilon subunit (in the immature form)
What occurs with spinal chord injuries
Sprouting occurs following by failed regen and degen, formation of cysts and glial scards,
Where is the largest number of neurones in the CNS
Cerebllum
Endoneurium
Around indiviudal axons within fasciles
What is the effect of enhanced of WNT signalling
Dorsal gene expression domain is expanded ventrally
What occurs for Ti1 –> Cx1 in mice lacking Sema3A
Axons able to stray into wrong territories
What induces receptor clustering
Basal lamina
What can be said of the recovery of connections in the spinal cord
Very poor
Describe nectin
Associated with ECM - like laminin, cells expressing the netrin gene can mimic the attractive nature of the floor plate
smooth brain - misencephaly
Loss of gyri and sulci
Fish and salamander lack
NOGO A
Incidence of medulloblastoma
500 births/year
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
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
When does synapse desity increase in the cat visual cortex
Around post natal day 10 - with the eyes open
What do posterior rhombic lip cells form
Pontine nuclei and inferior olive
What is the main attractive cue from the Fp
Netrins
Descirbe the hebbian synapse
Coordinated activity of a pre and post synaptic terminal strengthens the connection between them
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
What neurones found in the trigeminal nucelus
DiLA/DBLa neurones
What injury is likley to regrow bettwe with more accuratly
Crush
What is the effect of reduced WNT signalling
Ventral genes are expressed more dorsally
What are crucial for migration
Microtubules
What is the migraiton of newly born neuronal precurrsors
Lateral migration from VZ to the mantle zone where they diff
