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Neuroscience Unit 3 > Lecture 3: Axonal Growth, Synaptogenesis, and Tropism > Flashcards

Lecture 3: Axonal Growth, Synaptogenesis, and Tropism Flashcards

1
Q

What structure defines the polarity of the neuron? What is at the tip of this structure?

A

Axon

Growth cone

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2
Q

What is the growth cone and what does it do?

A
  • key decision-making structure in axon pathfinding during neuronal development
  • explores extracellular env, determines direction of growth, guides extension of axon
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3
Q

What two morphological characteristics are present in growth cones?

A

lamellapodium

filopodia

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4
Q

How is a lamellapodium characterized?

A
  • fan-shaped, tip of axon

- contains actin filaments and microtubules

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5
Q

How are filopodia characterized?

A

fine processes extending out from lamellapodia

  • contain actin filaments
  • form and disappear rapidly
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6
Q

What molecule is in both lamellapodium and filapodia?

A

F-actin

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7
Q

Where are tyrosinated microtubules found?

A

enriched lamellipodia

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8
Q

Where are acetylated microtubules found?

A

axons

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9
Q

What process is key to growth cone turning, and regulates retrograde flow?

A

F-actin binding proteins to F-actin

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10
Q

How do microtubules affect the core cytoskeleton in the axon?

A

stability, strength

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11
Q

What are the four types of axon guidance signals? Are the diffusible or non-diffusible?

A
  1. contact attraction - non-diffusible, short range
  2. contact repulsion - non-diffusible, short range
  3. chemoattraction - diffusible, long range
  4. chemorepulsion - diffusible, long range
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12
Q

Where do axon guidance molecules bind?

A

receptors on growth cones

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13
Q

What are non-diffusible attractive guidance molecules for growth cones in the PNS? To what do they bind?

A
  • laminins, collagens, fibronectin

- bind growth cone receptors = integrins

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14
Q

What are examples of non-diffusible guidance molecules in the CNS? Are these attractive or repulsive?

A

-aggrecan, hyaluronan, tenascin

repulsive –> inhibit cell movement/axon growth

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15
Q

Describe Cell Adhesion Molecules (CAMs)

A
  • located: surfaces (growing axons, growth cones, surrounding cells/targets)
  • non-diffusible
  • attractive (homophilic binding)
  • calcium independent
  • facsiculation (bundling) of axons
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16
Q

Describe Cadherins

A
  • located: surfaces (growing axons, growth cones, surrounding cells/targets)
  • non-diffusible
  • attractive (homophilic binding)
  • calcium dependent
  • actin binding and organization
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17
Q

Describe Semaphorins

A
  • secreted or anchored to cell surface
  • non-diffusible
  • mostly repellant
  • growth cone collapse, inhibition of axon extension
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18
Q

What are semaphorin receptors on growth cones? How do the surface and secreted forms bind to these receptors?

A
  • plexins
  • surface/anchored forms bind directly to plexins
  • secreted forms bind neurophilins, which then bind to plexins
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19
Q

Describe ephrins

A
  • on cells surface
  • non-diffusible
  • repellant
  • bi-directional signalling molecules
20
Q

How does ephrin A differ from ephrin B?

A

Ephrin A = GPI-linked to cell surace

Ephrin B = single-pass transmembrane proteins

21
Q

What does it mean that ephrins are bi-directional signaling molecules?

A

both growth-cone bearing cell and target cell will respond

22
Q

What signaling molecules guide projections from the retina to the optic tectum?

A

ephs and ephrins

23
Q

Axons in the developing temporal retina make connections with what portion of the tectum?

A

anterior tectum

24
Q

Axons in the developing nasal retina make connections with which portion of the tectum?

A

posterior tectum

25
Q

In what fashion are ephrins expressed in the optic tectum?

A

anterior-to-posterior gradient

26
Q

Describe how ephrins guide the correct projections from the temporal and nasal retina to the optic tectum

A
  • Axons from temporal retina have Eph receptor –> repulsed by ephrin in posterior tectum –> bind anterior tectum
  • Axons from nasal retina lack Eph receptor = blind to ephrin –> can bind posterior tectum
27
Q

Are netrins diffusible? What are receptors for attractive vs repulsive netrins?

A
  • Diffusible
  • Attractive receptors = DCC
  • Repulsive receptors = UNC5
28
Q

Are slits diffusible? Are the attractive or repellant? What are their receptors?

A
  • Diffusible
  • Repellant
  • growth cone receptors = Robo family
29
Q

Netrins play a key role in _____ crossing in the developing ______

A

comissural axon

spinal cord

30
Q

In comissural axon crossing: Comissural axons express 1____ and are originally attracted to the 2____, which produces high levels of netrin. As they cross the midline, they upregulate 3____, which keeps them from 4_____ because of the high levels of 5_____ at the midline.

A
  1. DCC
  2. midline
  3. Robo
  4. recrossing
  5. slit
31
Q

If two different axons use the same guidance cues, how is synaptic specificity achieved?

A

differential innervation of ganglionic neurons

32
Q

How do incoming axons preferentially form synapses on the correct targets?

A

pre- and postsynaptic neurons have higher affinity for each other

33
Q

Synaptogenesis at the neuromuscular junction:
Motor axon makes contact with 1____. Subsequent differentiation of the nerve terminal and myotube is induced by 2____, which activates 3____, causing clustering and increased local exp of 4_____ through the adaptor molecule 5______.

A
  1. myotube
  2. agrin
  3. Muscle activated kinase
  4. acetylcholine receptor
  5. rapsyn rapsyn
34
Q

In synaptogenesis at the neuromuscular junction, what do the nerve terminal and myotube differentiate into?

A

nerve terminal –> motor terminal

myotube –> postsynaptic apparatus

35
Q

In synaptogenesis at the neuromuscular junction, both the motor nerve and the muscle make ECM components to form a _____, which stabilizes the synaptic structure

A

basal lamina

36
Q

In synaptogenesis in the CNS, ____ helps localize cytoskeletal elements, synaptic vesicles, active zone proteins, and voltage gated Ca2+ channels to the _______

A

Neurexin

presynaptic membrane

37
Q

In synaptogenesis in the CNS, ____ recruits neurotransmitter receptors and other postsynaptic proteins to the ______

A

neuroligin

postsynaptic membrane

38
Q

How do target cells support survival and differentiation of neurons after synaptogenesis?

A

secrete neurotrophic factors in limited amounts

  • neurons compete
  • target cells help determine the # of cells which innervate them
39
Q

Nerve growth factor (NGF) is part of the _______ family

A

neurotrophin

40
Q

What are 4 pieces of evidence for the trophic function of NGF?

A
  1. absence of NGF –> neuronal death
  2. Increased NGF –> survival of excess neurons
  3. presence and production of NGF in target cells
  4. presence of NGF receptors in innervating nerve terminals
41
Q

What are three functions of neurotrophins?

A

1 survival of subset of neurons

  1. # target cells contacted
  2. # synapses formed
42
Q

Trk receptors and p75 receptor are _____ receptors

A

neurotrophin

43
Q

What are Trk receptors? What do they bind? What form of this molecule do they bind preferentially?

A
  • receptor tyrosine kinases

- bind processed (cleaved) neurotrophins only

44
Q

What is p75 receptor activated by? For what molecule does it have a high affinity?

A
  • activated by all neurotrophins

- high affinity for unprocessed neurotrophins

45
Q

What are the three cellular cascades which can occur from neurotrophin signaling?

A
  • cell survival or death
  • growth or differentiation
  • stabilization or elimination of synapses - activity-dependent

Neuroscience Unit 3 (8 decks)

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