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Biology 467 > Synaptogenesis > Flashcards

Synaptogenesis Flashcards

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1
Q

Briefly describe the important steps leading up to synaptic vesicle release

A
  1. Depolarization reaches synaptic bouton: Na largely mediates this
  2. AP reaches the Voltage-gated Ca channels
  3. Ca enters the cell
  4. Ca acts on vesicles causing them to fuse to the membrane
  5. Release of NT into the synaptic cleft
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2
Q

What is laminar specificity?

A

The specificity achieved by neurons projecting into different layers of a target tissue

e.g. spinal cord, IPL of the retina

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3
Q

How many kinds of bipolar cells are there?

A

~12

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4
Q

How many kinds of amacrine cells are there in the retina?

A

~19

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5
Q

In the IPL of the retina, what kinds of cell surface receptors are thought to mediate synaptic target specificity? (3)

A

Dscam, semaphorins, protocadherins

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6
Q

What molecule likely mediates 3o branch self avoidance?

A

mig-14, a homolog of wntless

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7
Q

When the mig-14/wntless pathway is activated, what occurs?

A

F-actin depolymerization causing retraction of 3o dendrites

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8
Q

Why are calcium indicator experiments useful for examining the formation of synapses?

A

Can examine where activity is (calcium = proxy for NT activity) particularly in filopodia to examine which projections make prolonged contact with synaptic targets

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9
Q

Explain what is happening in this graph

A

When filopodia grow and make contact with axons, the number of calcium transients increases to form a connection

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10
Q

Explain the takeaway from this image

A

When filopodia make stable contacts with an axon, calcium transients increase and synapses are more likely to form

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11
Q

Based on this information, what is a feasible hypothesis for what is happening when connections are being made?

A

Some kind of protein or signaling factor must be acting upstream of calcium influx to establish a connection between an axon and its synaptic target

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12
Q

Since filopodia stability precedes synapse formation, what does this suggest about the mechanisms which control synapse formation?

A

Must be regulated by cytoskeletal processes

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13
Q

What kind of staining is Cajal credited with inventing?

A

Golgi staining

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14
Q

Explain golgi staining

A

Stains the golgi bodies and is pretty good at targeting neurons specifically, although it tends to only target every few neurons not all of them

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15
Q

what kinds of neurons make connections with the cell bodies of purkinje cells?

A

Basket cells

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16
Q

Describe the axons of a basket cell and how they synapse to purkinje cells

A

Axons are all gathered around (and synapse to) the soma of purkinje cells and around the upper axon of purkinje cells

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17
Q

Describe how the specificity of basket cells synapsing to purkinje somas/upper axons is established

A

Neurofascin gradient around the soma which attracts axons, then axons attach to ankyrin G repeats around the AIS

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18
Q

AnkyrinG is a binding partner to (2)

A

Voltage-gated sodium channels and Neurofascin

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19
Q

What happens in purkinje neurons where ankyrinG is knocked out?

A

Axons of basket cells no longer preferentially synapse to the AIS

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20
Q

Name 4 levels by which specificity in synaptic target can be established

A

Laminar, cellular, subcellular, synapse-type

21
Q

What is an example of types of synaptic connections which are mediated by synapse type?

A

Neurexin/neuroligin complex

22
Q

Describe how prevalent the neurexin/neuroligin complex is

A

Expressed by most neurons

23
Q

Describe which synaptic membrane the neurexin/neuroligin are present on

A

Neurexin: presyn
Neuroligin: postsyn

24
Q

Describe how diversity/complexity is established among neuroligin/neurexin complexes

A

Neurexin on the presyn membrane has an alternatively spliced extracellular domain which conveys specificity

25
Q

Neurexin/neuroligin mediates (heterotypic/homotypic) interactions

A

Homotypic

26
Q

Alternative splicing aside, what are the 2 kinds of neurexin?

A

Alpha (long) and beta (short)

27
Q

What is the proposed difference between alpha and beta neurexin?

A

May regulate GABAergic/glutamatergic synapse formation

28
Q

Describe what SS#4 is with respect to neurexin

A

It is a 30 aa splice variant which the protein can be made with or without

29
Q

When the SS#4 variant of neurexin is present, the protein can interact with…

A

NMDR, a glutamate receptor

30
Q

Without the SS#4 variant, neurexin cannot interact with (1) but it can interact with (2, 3)

A
  1. Neuroligin
    2/3. CAN interact with NMDR and AMPA glutamate receptors
31
Q

The working hypothesis about neurexin complexes suggest that different neurexin ligands organize different…

A

Types of synapses

32
Q

Name 9 kinds of molecules present on the postsyn neuron membrane which could be mediating synapse specificity

A

Neuroligins
Cadherins
AnkyrinG/Neurofascin
SynCAM
Protocadherins
TrkB
LAR-RPTP
Dasm1
NCAM

33
Q

Name 5 kinds of molecules present on the presyn neuron membrane which could be mediating synapse specificity

A

alpha/beta neuroexins
SynCAM
Protocadherins
Cadherins
CPG14

34
Q

Name 6 kinds of molecules present in the soluble/extracellular synaptic cleft which could be mediating synapse specificity

A

Laminin
Versican
Thrombospondin
FGF22
Heparin sulfate
Proteoglycans

35
Q

Why is the neuromuscular junction a good model for studying the development of the axon-dendrite synapse? (3)

A

Large size
Accessible
Simple organization

36
Q

Dendritic filopodia and dendritic spine motility is regulated in part by these two molecules (2) that act on…

A

TrkB and EphB2, act on F-actin dynamics

37
Q

What ligand acts on muscle-specific tyrosine kinase receptors (MUSK) at the NMJ?

A

Agrin

38
Q

Activation of MUSK stimulates…

A

Clustering of acetylcholine receptors

39
Q

Monomers of MUSK are called…

A

LRP4

40
Q

Within the NMJ, the active zones surrounding a muscle fiber are arranged in…

A

An outside-in manner

41
Q

Adjacent to the active zone, there is the (1) zone

A

Peri-active

42
Q

What is a key receptor on the postsynaptic side of the peri-active zone?

A

Shaker

43
Q

What binds to shaker?

A

Dlg - scaffold protein which arranges cells close together so that a correct synapse can occur

44
Q

Lining the inside of the postsynaptic membrane are the important cytoskeletal proteins… (2)

A

alpha and beta spectrin

45
Q

Describe the importance of beta spectrin

A

Ensure proper synaptic proteins are localized to a region where synaptic activity is occurring to ensure exposure to neurotransmitter – helps link proteins to the cytoskeleton

46
Q

The Gal4-UAS system is derived from…

A

Yeast

47
Q

Describe the Gal4-UAS system briefly

A

Gal4 can be placed downstream of a promoter, and when transcribed/translated will bind to UAS to activate a gene which is downstream of UAS, this could be a gain/loss of function, or GFP for example

48
Q

In the Gal4 system, there is usually a cross between X-Gal4 and UAS-Y, where X and Y are target genes. Which of these two lines is the “driver” line?

A

X-Gal4

49
Q

What is the primary utility of the Gal4 system

A

It is an inducible model: can be used for conditional knockouts, etc.

Biology 467 (20 decks)

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