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Neurobiology > Neuronal Cell Biology > Flashcards

Neuronal Cell Biology Flashcards

1
Q

neuronal doctrine

A

1) neurone is structural and funcitonal unit of NS
2) neurones are individual cells not continuous to other neurones (some are, so wrong)
3) 3 parts - dendrites, soma, axon
4) conduction from dendrites to soma (polarity)

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2
Q

initial segment (axon hillock)

A

AP origin

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3
Q

dendritic spines

A

blebs, post-synaptic elements, synapses with axon, lots activity in env means lots spines so plasticity, receive input from axon but signals can travel both ways

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4
Q

longest human neurone

A

just over 1m

so instead of moving things, you synthesise locally and derive products from other cells

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5
Q

retrograde

A

terminals up axon to soma
5mm a day
transport absorbed material or degraded membrane

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6
Q

anterograde

A

soma down axon to terminals

300-400mm a day / 5-10m

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7
Q

what is used for axonal transport

A

with neurofilaments, microtubules, motor proteins with ATP

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8
Q

Amyotrophic lateral sclerosis (ALS)

A

Stephen Hawking

is transport goes wrong, loss function in motor neurones, so degenerate because not active

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9
Q

local protein synthesis evidence

A

if inactivate neuronal enzyme then should be in axon according to proximo-distal gradient if everything is moving
expect greater activity where made and little long distance away but this wasn’t the case, both ends had equal rates of recovery of enzyme so mRNA of enzyme moving

some proteins are in synaptosomes but depleted in cell body so not made in cell body

transfect isolated dendrites - inject mRNA should translate if have all correct things for it

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10
Q

axonal transport

A

3’ untranslated regions on mRNA signal to carry it by motor proteins to post-synaptic density
lots mRNAs in dendrites
neuronal activity regulated translation and protein targeting

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11
Q

nanotubes

A

connect cells so neurones share using motor proteins

can move mitochondria from healthy to damaged neurones

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12
Q

glial cells

A

most abundant cell in CNS
surround neurones for support
role in synapse - can release NT
e.g. astrocyte, microglia, oligodendrocyte

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13
Q

astrocyte

A

mop up NTs, keep correct ionic env

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14
Q

microglia

A

scavengers

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15
Q

GFAP

A

glial fibrillary acidic protein
marker for glia
intermediate filament protein in glia

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16
Q

oligodendrocyte

A

forms myelin sheath

in CNS wrap over 50 neurones

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17
Q

what are synapses made up of

A

tripartite

so 2 neurones and glial cells

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18
Q

gap junctions

A

neurones electrically connected, don’t need NT

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19
Q

exosomes

A

share through extracellular vesicles

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20
Q

myelin is only in..

A

vertebrates because invertebrates make neurones bigger for faster transmission

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21
Q

myelin function

A

saltatory conduction (ions out at node only)
increases conduction velocity - 10x faster
insulated neurones
DONT MENTION SKIPPING

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22
Q

schwann vs oligodendrocytes

A 
schwann cell (in PNS) wraps round 1 neurone
oligo wraps 50, more flexible (in CNS)
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23
Q

myelin structure

A

wraps and spiral from inside out for compaction (done by proteins)

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24
Q

immunoglobin superfamily:
MBP
PLP, PMP-22, Po
MAG

A

myelin basic protein (in CNS)
huge +ve charge so attract everything together and drive compaction of myelin

PLP in CNS, PMP-22 and Po in PNS, same job, link lipid layers to wrap myelin

myelin associated glycoprotein (in CNS and PNS, more in CNS)
tucking under to start spiralling inside (initiation)

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25
Q

EAE (experimental autoimmune encephalomyelitis)

A

mouse model for multiple sclerosis

affects T-helper lymphocytes,invade PNS/CNS so demyelinate

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26
Q

demyelination

A

cause over 50 neuropathies like MS etc.
adrenoleukodystrophy is target for gene therapy
can remyelinate with stem cells

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27
Q

axonal guidance

A

process by which neurons send out axons to reach their correct targets

3 levels (pathway, target, address)
identify what neurone is, make neurite with growth cone, receive signals so migrate to roughly right place (target) then makes selection (address)
28
Q

cerebellum axon guidance

A

millions of same units synapses with big purkinje cell so makes connections with very defined neurones
granule cells in cerebellum make a million synapses into 1 purkinje cell (purkinje recieve impulses from granule)
mossy fibres only make 1 synapse

29
Q

neurite and growth cone

A

is not yet axon and synapse because not electrically active yet

30
Q

growth cone

A

actin+microtubule extension of developing neurite, seeking synaptic target
has instructions for finding route
sensing and movement
can carry on if cut cell body off

31
Q

treadmilling

A

10-20um in 7 mins (not quick)
adhesion
membrane addition
actin polymerisation

32
Q

adhesion (axon movement - treadmilling)

A

filopodia with microtubules stressing behind it (inside) so extend into it
filamentous actin on tip of filapodia
ECM with adhesive things
receptors (which bind substance) bind ECM inside (connected to filapodia)

2 roles - growth (attach to substrate) and guidance (navigation)
receptors on surface of growth cone touching adhesive properties of ECM that are guidance and target signals

33
Q

membrane addition

A

F-actin can treadmil

move membrane from part of filopodia to the front

34
Q

actin polymerisation

A

(after adhesion and membrane addition) THEN bind to next receptor to next adherence molecules
senses adherence molecules on surface, transmits signal to actin and moves it
actin treadmils, membrane moves, filapodia moves, is quick

35
Q

ladder pathways

A

pathways in Drosophila embryo where neuroblasts divide and make neurones, sending projections up/down/across
midline is middle of ladder
BP102 Abs show ladder
rungs of ladder segmentally repeated

36
Q

mutations lacking guidance molecules in Drosophila

A

no ladder

  1. roundabout - few longitudinal fascicles
  2. commissureless - nothing in middle (ones that cross are called commissures so lacking)
37
Q

fascicles

A

bundle of structure of nerve

38
Q

examples of pathways of Drosophila guidance molecules

and mutations

A

Ap in wt goes up and stays ipsilateral (on the side) on same side
pCC very ipsilateral
SP1 project contraleteral (cross to opposite side) then up

axon guidance tells to cross/not cross middle/edge

robo mutation everything crosses midline
comm mutation nothing crosses midline

39
Q

axon navigation

A
  1. neurone identified by signalling/TFs - knows has to get to target A
  2. receives signals on the way like a relay, attractant molecules like netrin as well as adhesion molecules
  3. can be inhibitory molecules, same ones but act diff to diff neurones
40
Q

target recognition

A

when get to target, stick to address with adhesion

41
Q

guidance molecules examples

A

N-cadherin in EM (close neural tube), MAG (tucks myelin), DCC (receptor for slit), EPH (organise projections through eye)
Robo receptor

42
Q

Robo receptor (roundabout)

A

on membrane (transmembrane receptor), binds to stuff, guidance by repulsion
mutation means lose repulsion from midline so go round and round
(slit ligand for robo in Drosophila affects guidance in embryo)

43
Q

repulsion

A

growth cone grow towards neurone, contact, collapse back and repel but leaves contact but massively goes back - dynamic instability
(axon guidance repulsion)

44
Q

netrin

A

attractive cue attracts neurones towards midline

cells (mostly glial) sit on midline and secrete netrin

45
Q

slit

A

mRNA in same cells as netrin
so attract some neurones, repel other
slit mutant is like robo mutant

46
Q

comm

A

Controls axon guidance across the CNS midline by preventing the delivery of Robo to the growth cone

comm on - binds to robo and directs it to lysosome for destruction, no robo so no receptor for slit so cross midline because attracted to netrin and robo can’t repel, but once crossed comm is downregulated so can’t go back

comm off - robo on so don’t cross

47
Q

comm mutation

A

comm always off
no crossing
always ipsilateral side

48
Q

robo mutant

A

always cross so roundabout

49
Q

robo in drosophila

A

has 3 robos responsible for each tract (3 lines going up)

which pathway depends on which robo (middle, inside, outside)

50
Q

guidance is different in vertebrates (mammals)

mutations

A

no comm
contralateral sensory neurone cell body sends projection to floor plate
sonic hedgehog attractant in midline
every projection crosses floor plate (like midline in fruitfly)
robo and slit important
3 robos encode cell surface molecules
robo 3 changes isoforms (3.1 3.2)

just robo 3 is null so never crosses midline, if knockout all robo it’s same as wildtype

51
Q

synaptic refinement purpose

A

adhesion molecules and code is not enough to wire NS (target)
need activity to refine synaptic connections (address)

52
Q

Sperry and Cajal

A

Sperry did epilipsy, cut hemispheres, evidence for Cajal’s neuronal interconnections from chemical recognition

53
Q

structure of optic pathway

A

optic nerve to lateral geniculate nucleus (tectum), nerves cross optic chiasma, 2nd order neurones from tectum, connections to visual cortex in back of brain

projections from retina to tectum - anterior of retina to posterior of tectum and posterior retina to anterior tectum

54
Q

frog evidence (Sperry)

A

frog optic nerve cut out and switched round so image other way round

showed that not learn from exp but is genetic
because changing optic nerve placement still went to same pathway so changed how you see and didn’t adjust

55
Q

ephrin

A

ligand

secreted by tectum, project through optic nerve, direct to right area of tectum

56
Q

chemospecificity hypothesis

A

neurons make connections with their targets based on interactions with specific molecular markers and, therefore, that the initial wiring diagram of an organism is (indirectly) determined by its genotype.

57
Q

problems with chemospecificity hypothesis

A

experience and neuronal activity plays some role
don’t know code - would need huge no. combinations if each connection required diff molecule
doesn’t explain learning

BUT DSCAM gene in drosophila could explain hypothesis (but still problems with it)

58
Q

DSCAM

A

lots exons so alternatively spliced, so enormous and could explain chemospecificity
but splicing only in some insects
mutation - not much happened in neural tubes in mammals only retina (amacrine cells in retina lose repulsion so stick together), not much splicing

59
Q

vision - eyepatch kitten experiment

A

radioactive tracer in eye
2 weeks - tracer is uniform in layer 4C (3rd order synaptic connections)
3 weeks - change
5.5 weeks - segmenting
13 weeks - ocular dominance columns (stripes of neurones)

if both eyes blind - uniform distribution so not natural columns, need experience
so retinal activity required for precise synaptic connectivity in visual system (to make columns)

patch over 1 eye - inputs dominate from open eye

60
Q

ocular dominance columns

A

stripes of neurons in the visual cortex of certain mammals that respond preferentially to input from one eye or the other

61
Q

plasticity mouse evidence

A

deprived/bored –> neurones degenerate, pruned, less active, less receptors
so activity required for neuronal growth and underlies learning

62
Q

aplysia

A

large sea slug

shows how learning changes neurones and receptors change density

63
Q

axons that fire together..

A

wire together

2 fires simultaneously will consolidate and synapses become stronger

64
Q

neurotrophins

A

secreted protein required for neuronal survival
signal to cells to survive differentiate and grow

acts as reward for neurone being active (plasticity) retrograde release from postsynaptic when pre signals to post
so if 2 neurones then more reward (consolidate strength)

65
Q

venom exp

A

into fertilised chicken eggs, drive formation of neurones so nerve growth factor in venom

66
Q

neurotrophin experiment

A

Ab against BDNF (brain derived neurotrophic factor) caused uniform distribution of tracer like in both eyes blind exp. so blocks reward circuit

Neurobiology (4 decks)

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