Lecture 4: Construction of Neural Circuits Flashcards

1
Q

Neuronal polarization

A

The formation of axons and dendrites

As neuroblasts/ immature neurons complete their migration, they extend axons and dendrites guided by scaffolding cells and molecular gradients (POLARIZATION)

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2
Q

IN CULTURE neuronal polarization (based on in vitro observation):

A

Stage 1: lamellipodia surrounding periphery
Stage 2: appearance of ‘symmetric’ neurites
Stage 3: break of symmetry by differential growth rate
Stage 4: remaining neurites become dendrites
Stage 5: final mature neuron

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3
Q

neurites become

A

dendrites

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4
Q

Formation of Axons and Dendrites steps

A
  1. Symmetry breaking cue (local signals, eg: secreted molecules)
  2. Local signal amplification (expression of PAR proteins, polarity regulator, and signalling of future axon)
  3. Cytoskeletal rearrangement (cytoskeletal redistribution and establishment of polarity)
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5
Q

Neuronal polarity

A

axon and dendrites are structurally (and functionally) different

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6
Q

Axons:

A

microtubule + ends out (away from soma) -end towards soma

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7
Q

Axons -
Kinesin (anterograde transport) + Dynein (retrograde transport)

A

motor proteins for anterograde and retrograde transport via MT tracks (more particles/vesicles from/to soma)

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8
Q

Dendrites

A

MTs (microtubules) of mixed polarity (+/- ends mixed, some out and some inwards)

Golgi outposts (proximal) and satellites (distal) contribute to dendritic outgrowth

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9
Q

F-Actin in Dendrites

A

serve as tracks for local transport of mRNA and proteins to dendritic spines by Myosin V (myosin binds to actin, binds to dendritic spines)

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10
Q

Neuronal Growth Cones:

A

specialized structure at the tip of a growing neurite (Highly motile), exits in dendrites, not fully differentiated
- Critical for sensing environment and finding targets

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11
Q

what are the components of neuronal growth cones

A

lamellipodium = Expansion of the cone (tubulin)
filopodia = Finger-like projections at the distal tip (actin)

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12
Q

Chemotaxis = chemotropism

A

the attraction or repulsion of growth cones (senses environment cues to determine final destination) by certain molecule

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13
Q

Chemoattractant : Diffusible signals (long range):

A

Form a concentration gradient
e.g., (+) netrin; slit
e.g., (-) semaphorin

tropic

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14
Q

Chemorepellent: Non-diffusible signals (short range):

A

e.g. (+) ECM proteins (laminin, fibronectin) with cell membrane-bound integrins
e.g. (+) Cell adhesion molecules (CAMs, cadherins)
e.g. (-) Ephrins (can be chemoreplants or opp. effect)

tropic

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15
Q

Extension and change in direction require (The molecular basis of growth cone motility)

A

depolymerization and polymerization of tubulin (lamillopodium and shaft) and actin (leading edge of lamillopodium and filapodia) axon needs to determine where to go, helps neuron migrate and reach final synapse
- ATP-dependent

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16
Q

what is growth cone motility regulated by

A
  • Attractive and repulsive cues
  • actin and tubulin binding proteins
  • changes in [Ca2+]I via voltage-gated Ca2+ channels, transient receptor potential (TRP) channels and/or internal stores
17
Q

Ca2+ is important for in Growth cone behavior and axonal growth:

A
  1. Axonal and cone growth
  2. Turning when approaching its target:
    - Ca2+ release from the ER guides polymerization and attraction
    - Ca2+ influx from the extracellular space (through Ca2+ channels) induces depolymerization (breaking down microtubules and actin filaments) and repulsion
18
Q

Growth cone wants to grow towards

A

chemoattraction (needs depolarization)

19
Q

Polymerization:

A

actin filament grows

20
Q

Depolymerization:

A

actin filament doesn’t grow

21
Q

Polarized dendritic growth ALSO relies on extrinsic signal

A

Semaphorin 3A (can be short-range, not secreted, or secreted and released, long range) acts as both a chemoattractant (dendrites) and a chemorepulsive (axon) signal based on the activity of a soluble guanylyl cyclase (sGC - receptor) that is available in dendrites but not in axons

22
Q

main events of the construction of neural circuits

A

Main events:
* Neuronal migration to final destination
* Neuronal polarization (part of differentiation)
* Apoptosis (Initial refinement – tropic
support dependent)
* Synaptogenesis
* Myelination
* Synaptic pruning and further
refinement/modification to generate mature
circuits

23
Q

PAR protein

A

(polarity regulator) - singling of future axon

24
Q

tropic vs trophic molecules

A

“tropic” hormones target other endocrine glands (cams, ephrins, ecm..) , while “trophic” molecules promote growth, survival, and differentiation of target cells, often in the nervous system (NGF)

25
Q

MT

A

microtubule (hollow, with alpha and beta tubulin)

26
Q

MF

A

microfilaments (two intertwined F-actin chains, G-actin)

27
Q

Ca2+ important for…

A

depolymerization