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Developmental Neurobiology > Glia In The Developing Nervous System > Flashcards

Glia In The Developing Nervous System Flashcards

1
Q

Glia types

A

Radial glia
Microglia
Ependymal cells
Astrocytes
Oligodendrocytes and OPCs

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2
Q

Roles of radial glia

A

-developmentally transient (not in mature brain)
-neurogenesis
-guide migration
-connectivity
-in cortical development/retinal muller glia/cerebella’s Bergman glia

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3
Q

Radial glia neurogenesis

A

Polarised neuroepithelium undergoes interkinetic nuclear migration and divides symmetrically
Loss of ZO1+ tight junctions and decreased FGF10 cause neuroepithelium to form ventricular radial glia in VZ

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4
Q

Radial glia division

A

Early RG expand symmetrically to expand pool
RG undergo asymmetric division to produce IP (delaminate to SVZ) and self renew to from neurons

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5
Q

how do radial glia direct neurogenesis

A

neurons migrate to the cortical plate via RG basal processes as a scaffold

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6
Q

what is a RG detachment cue

A

sparc like 1 SC1 in cortical plate

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7
Q

what type of migration do excitatory neurons undergo

A

radial migration

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8
Q

what type of migration do inhibitory interneurons undergo

A

tangential migration

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9
Q

how to RG inhibit axogenesis

A

RG interact via N-cadherin to drive RhoA

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10
Q

how to RG promote axonogenesis

A

RG use Rac1 (trailing process)

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11
Q

how to RG influence connectivity - experimental procedure
(Yu et al., 2009)

A

in utero retrovirus (selectively produces dividing cells)
sparsely label clonally related sister cells
simultaneously record sister cells (red and green) and unlabelled neighbouring cells (red only)

greater connectivity probability in sister cells

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12
Q

microglia roles

A

main CNS resident macrophage (1st line defence)
surveillence and engulfment of pathogens
professional sensors at chemical interference of brain and body
adopt distinct states depending on context

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13
Q

how is microglia formed

A

from yolk sac (YS) erythromyeloid progenitors (EMP)
migrate to brain in blood and arrive before BBB closes
EMPs differentiate and self renew to microglia

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14
Q

what does microglia survival and differentiation require

A

CSF-1R (receptor) activation by IL-34 (from neurons and or CSF1 (astrocytes/OL) and TGFbeta signalling from astrocytes

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15
Q

which cells do microglia remove

A

microglia engulf cortical neuronal precursor

microglia promote cell death - purkinje cells undergo apoptosis (marin-teva et al., 2004) CaBP stains for purkinje cells (main projection cells in cerebellum)

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16
Q

how do microglia prune synapses

A

activity dependent segregation in mouse dLGN in thalamus - sharp C and I border (Guido, 2018)

Gabaergic synapses pruned by microglia via phagocytosis requires CR3-C3 signalling

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17
Q

how do microglia promote synaptic strength in the olfactory system

A

CSF1R inhibitor (PLX5622) then GCamp injection - smaller responses to olfactory stimulation and less excitation
no effect of microglia depletion if done after abGC maturation

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18
Q

how do microglia cause synaptic remodelling

A

clearance of dense ECM

19
Q

how to microglia restore ocular dominance plasticity (Venturino et al., 2021)

A

perineuronal net formed around PV+ inhibitory interneurons and ends critical period

microglia can breakdown perineuronal net via ketamine anaesthesia/60Hz light entrainment

restores ocular dominance plasticity

20
Q

what do ependymal cells consist of

A

ciliated simple cuboidal epithelium

21
Q

ependymal cells roles

A

regulates blood-CSF interactions at choroid plexus
line ventricles for CSF-brain interactions
CSF dynamics via beating cilia in ventricular space

22
Q

ependymal cells development

A

derived from RG (E16-18)

form cilia and adhesion molecules for barrier formation and joining

ependymal cells position into rossette structures surrounding CSF, contacting tips of adult NSC

23
Q

how do ependymal cells direct neuronal migration

A

neuroblasts in adult SVZ follow RMS CSF flow via beating cilia

orpk mutants - few/short/irregular cilia. disordered migration of neuroblasts

CSF deposits slit2 gradient caudally, slit2 repels neuroblasts

24
Q

astrocyte roles

A

maintain BBB via end feet
regulate and support neurotransmission
metabolic support
SC pool

25
Q

wave 1 (prenatal) of astrocyte development

A

late development (after microglia)

cortical SVZ RG form neurons (asymmetrical division)

RGs form translocating RGs E16.5 (requires EGFR and cytokine expression)

tRG use radial migration to form astrocyte progenitor cells
APCs undergo symmetrical division to produce astrocytes

26
Q

wave 2 (postnatal) of astrocyte development

A

cortical SVZ RG produce IP (EGFR and Ascl1 upregulation)

basal multipotent IPCs (bMIPCs) proliferate rapidly

bMIPCs express both astrocytes (Glast) and OL (olig1/2) markers

OPCs - downregulate EGFR
APCs - maintain EGFR

27
Q

astrocytes and neuronal migration

A

thalamic astrocytes produce downstream components of Shh

deletion of shh
decreases FGF15 mRNA
decreases % of interneurons recruited into visual thalamus (less GAD1 (GABA production))

28
Q

how do astrocytes cause synaptogenesis

A

B cells (astrocyte SC contact CSF)

C cells

A cells

29
Q

TSP KO in retinal ganglion cells

A

reduces synaptic terminals (astrocytes)

30
Q

B1 astrocyte stem cells

A

produced E13.5-15.5 remain quiescent until reactivated postnatally

31
Q

astrocytes and ependymal cells have the same lineage

A

GEMININ = more astrocytes
GEMC1 = more ependymal cells

32
Q

oligodendrocyte roles

A

insulation - increased membrane resistance , fast saltatory conduction at nodes of ranvier

metabolic - supply mitochondria with substrates for oxidative phosphorylation

33
Q

schwann cells vs OLs

A

schwann cells myelinate just one axon
OLs myelinate many axons

34
Q

development

where do OLs arise from

A

bMIPCs in cortex to form OPCs
OPCs populate both white and grey matter

35
Q

name OPC markers

A

OLIG2
NG2
PDGFRa+
NKX2.2

36
Q

name myelinating OL markers

A

OLIG2
GalC
CNPase
MBP
MAG
MDG

37
Q

how do myelin sheaths form

A

neurofascin clusters accumulate prior to myelination
neurofascin located at the nodes of ranvier

38
Q

role of neurofascin

A

sets myelin position/cell adhesion molecule

39
Q

learning dependent myelin dynamics

Bacmeister et al., 2022

A

adult mice trained on forelimb task
tdT = active cells in L2/3 neurons dependent on c-fos expression
changes node length

40
Q

where do OPCs prune synapses

A

thalamus only
OPCs internalise presynaptic structures

41
Q

what maintains myelin

A

microglia

42
Q

what occurs in human adult onset leukoencepalopathy

A

reduces microglia
age related demyelination

43
Q

how do OPCs migrate

A

use blood vessels
OPCs receive inhibition from blood vessel niche to prevent OL formation

44
Q

how do astrocytes prevent OPC perivascular migration

A

astrocyte endfoot placement
astrocytes produce semaphorins 3a and 6a - repel OPC from blood vessels to detach and myelinate

endothelium niche prevents OPC differentiation. OPC detach to allow differentiation

Developmental Neurobiology (19 decks)

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