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NEUR 2000 > Lecture 15: Synapse Formation > Flashcards

Lecture 15: Synapse Formation Flashcards

1
Q

What structure sends signals to overlaying ectoderm to signal neural tissue formation?

A
  • Notochord

- “causes formation”

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2
Q

What happens after the formation of the neural tube?

A
  • Neurogenesis
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3
Q

What do neural cells most commonly follow in neural migration?

A
  • Radial glial fibres
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4
Q

What determines which target cells to innervate?

A
  • Cell-cell attractions

- Cues to drive attractive forces

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5
Q

Is the process of synaptogenesis rigid or flexible?

A
  • Generally very flexible

- Some restrictions

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6
Q

What are the restrictions on synaptogenesis?

A
  • No synapses with glial cells in CNS

- No synapses with connective tissue in PNS

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7
Q

What are the 3 stages in forming synaptic connections?

A
  • Initiation
  • Induction (with chemical signals)
  • Reinforcement (strengthening/growth or synaptic pruning/apoptosis)
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8
Q

When does synaptogenesis begin?

A
  • Once an axon reaches its target region
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9
Q

How precise is initiation of synaptogenesis?

A
  • Imprecise

- Guided by graded system of preferences (not absolute)

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10
Q

What does initiation of synaptogenesis consist of?

A
  • Recognition b/n proteins on pre- and post-synaptic cells
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11
Q

What makes potential connections b/n potential pre-and post-synaptic sites?

A
  • Share many molecules

- Includes many adhesion molecules that participate in axon guidance (cadherins, protocadherins)

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12
Q

What is the initiation of synaptogenesis mediated by?

A
  • CAMs (cell adhesion molecules; cadherins, protocadherins)
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13
Q

What do CAMs do in the initiation of synaptogenesis?

A
  • Link pre- and post-synaptic domains as proteins recognized
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14
Q

What is there initially an accumulation of in the initiation of synaptogenesis?

A
  • Synaptic vesicles and transport vesicles that contain molecular components of presynaptic active zone
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15
Q

What is induction in synaptogenesis?

A
  • Construct architecture to maintain synapse
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16
Q

What is the role of CAMs in induction?

A
  • Elaborate on cellular specialization
  • Form structural components of the synapse by recruiting cytoskeletal proteins to form synaptic shape
  • Localize synaptic vesicles
  • Cluster postsynaptic receptors
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17
Q

What are 5 inductive factors?

A
  • SynCAM
  • Ephrin B/EphB-R
  • Neurexin
  • Neuroligin
  • Neuregulin
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18
Q

Where are neurexins and what do they do?

A
  • In presynaptic membrane
  • Specialized transmembrane domain helps localize vesicles, docking proteins and fusion molecules
  • Localizes voltage-gated Ca2+ channels vital for vesicle release
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19
Q

Where are neuroligins and what do they do?

A
  • In postsynaptic membrane
  • Interact with specialized postsynaptic proteins to promote clustering of receptors/channels of postsynaptic density
  • Maximize synaptic signalling
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20
Q

Where is neuregulin 1 found and what does it do?

A
  • Made in synapse, cleaved, then acts on postsynaptic ErbB receptors
  • Regulates expression and localization of other postsynaptic receptors (human NRG1 gene associated with schizophrenia)
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21
Q

What does the interaction of neurexin with neuroligin do?

A
  • Central for recruiting and retaining cytoskeletal elements that localize synaptic vesicles to the presynaptic terminal and mediate their fusion
  • Ensure post-synaptic membrane has proper receptors available
  • Shared by all developing synapses
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22
Q

What are genetic polymorphisms of neurexin or neuregulin related to?

A
  • Autism and schizophrenia

- Dysfunction in these CAMs can affect entire CNS

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23
Q

What are some likely players in synaptic identity/differentiation?

A
  • DSCAM1
  • Ephrin ligands and receptors
  • Other CAMs
  • Mutation effects
  • Protocadherins
24
Q

What effect is DSCAM1 thought to have on differentiation?

A
  • Similar process that mediates dendritic tiling may prevent a cell from forming synapses with itself
  • Chemorepellant signals to keep a space
25
Q

What effect are ephrin ligands/receptors thought to have on synaptic identity?

A
  • Diverse population may be differentially distributed

- Cell-cell recognition

26
Q

When it comes to synaptic identity, what are CAMs thought to do?

A
  • Multiple sites for alternative transcript splicing can encode many variants of the same basic protein with differential distribution
27
Q

What effects might mutations have on synaptic identity?

A
  • Unexpected

- Subtly disrupted connectivity patterns

28
Q

What might protocadherins do in synaptic differentiation?

A
  • A diverse array of CAMs arising from a single gene
  • Not uniformly expressed in neighbouring synaptic sites
  • Adherence/affinity relies on degree of similarity b/n proteins and neighbouring cells
29
Q

What kind of scale are synapses formed on?

A
  • Probability
30
Q

What is the reinforcement of synaptogenesis dependent upon?

A
  • Trophic interaction b/n pre- and post-synaptic cells (apoptosis vs. growth)
31
Q

What do neurotrophic factors do in reinforcement of synaptogenesis?

A
  • Secreted in relatively small quantities from target tissues
  • Regulate differentiation, growth, and survival in nearby cells
  • Don’t diffuse far, so they are hard to identify
32
Q

What are 4 neurotrophins involved in the reinforcement of synapses?

A
  • Nerve growth factor
  • Brain derived neurotrophic factor
  • Neurotrophin 3
  • Neurotrophins 4 and 5
33
Q

What is an example of a role that nerve growth factor (NGF) plays in reinforcement?

A
  • Elicits robust growth of neuronal processes (neurites) on sympathetic neurons
34
Q

What is an example of BDNF’s function in reinforcement?

A
  • Supports survival of sensory ganglion cells
35
Q

What role might NT-3 play in reinforcement?

A
  • Supports sympathetic and ganglion neurons (combination of NGF and BDNF)
36
Q

What might NT-4/5 support in reinforcement?

A
  • Neurite extension on cerebellar neurons
37
Q

What does the neurotrophin excreted depend on?

A
  • Synaptic identity/differentiation
38
Q

When in life do axons synapse onto more target cells?

A
  • Birth (more than maturity)
39
Q

What happens to immature contacts? Why?

A
  • Removed with development
  • Leaving a focus on fewer target cells
  • Progressively increasing amount of synaptic machinery for each axon that remains
  • Creates a stronger connection
40
Q

Describe the developing nervous system?

A
  • Initial surplus of cells

- Limited trophic support

41
Q

What happens to cells that fail to interact successfully with targets?

A
  • Undergo apoptosis
  • Regulated process that results in cell death
  • Mediated by neurotrophic factors
42
Q

How can a population of afferent neurons be appropriately matched to its target? List 3 assumptions.

A
  • Neurons depend on a minimum amount of neurotrophic factor for survival and connections
  • Target tissues synthesize appropriate trophic factors and make them available to developing neurons
  • Survival, persistence, differentiation of developing neurons are subjective to interneuronal competition for available factor
43
Q

What happens when chick sensory ganglion cell is incubated in absence of NGF?

A
  • Minimal neuronal branching/process outgrowth
44
Q

Describe trophic factors in general

A
  • Similar function
  • Encoded by distinct genes
  • Act in different places (ex. dorsal root ganglia vs. nodose ganglia vs. sympathetic ganglia)
45
Q

Where does NGF promote neurite growth?

A
  • Dorsal root ganglia
  • Sympathetic ganglia
  • NOT nodose ganglia
46
Q

Where does BDNF promote neurite growth?

A
  • Dorsal root ganglia
  • Nodose ganglia
  • NOT sympathetic ganglia
47
Q

Where does NT-3 promote neurite growth?

A
  • Dorsal root ganglia
  • Nodose ganglia
  • Sympathetic ganglia
48
Q

How are neurotrophins similar to neurotransmitters?

A
  • Neurotrophins activate receptors
  • Receptors influence action of neurotrophins
  • Only have function in trophins act on receptors
49
Q

What do specific Trk receptors have a high affinity for?

A
  • Processed (proteolytic cleavage) neurotrophins
50
Q

What do p75 receptors have a high affinity for?

A
  • Unprocessed neurotrophins

- Low affinity for processed

51
Q

What likely contributes to specificity of neurotrophic interactions?

A
  • Very specific cell neuronal expression and localization
52
Q

What kind of receptors are neurotrophic receptors?

A
  • Metabotropic (trigger G protein)

- Transmembrane domains, NOT ion channels

53
Q

How do filopodia/lamellipodia guide the growing process?

A
  • They adhere to substrates in extracellular environment

- Respond to guidance cues

54
Q

Is a certain chemical always seen as a chemorepellant?

A
  • No, it may be a chemoattractant for another growth cone
55
Q

What do cells compete for in order to survive?

A
  • Formation of adequate synapses

- Trophic factors

NEUR 2000 (10 decks)

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