L3 Synapse Formation & Elimination Flashcards
Where has the bulk of study on synapse formation been done?
Neuromuscular synapse (much larger than central synapse - easier to manipulate)
What is the neurotransmitter at the NMJ?
ACh
What increase surface area for AChR clusters?
Post-junctional folds
Synapse formation requires…
contact, AChR clustering, weeks to mature
Signals for pre- and post-synaptic differentiation localised to…
synaptic basal lamina
What is the basal lamina?
A strong, fibrous, permeable matrix that acts primarily as a base on which cells in the body can grow (also links cells together and to underlying CT)
Neuromuscular transmission
release of ACh from nerve terminal and activation of ACh receptors in postsynaptic membrane
Neuromuscular synapse formation in vertebrates
Primitive, aneural AChR clusters prior to arrival of phrenic nerve terminals distributed in a broad region in the middle of muscle fibres. Innervation leads to appearance of large AChR clusters in the synaptic region & disappearance of primitive clusters in non-synaptic areas
What protein is released to initiate synapse formation once an axon has arrived at its desired location?
Agrin
What is agrin a signal for?
post-synaptic differentiation
What do anti-agrin antibodies do?
block AChR clustering
Agrin initiates…
AChR clustering
True or False: In the NMJ, agrin secreted by the neuron is trapped by the basal lamina.
True
What happens to agrin -/- mice?
They lack normal synapses due to a reduction in AChR clusters, and therefore die after birth due to faulty diaphragm
Why is there inter-axonal competition for synaptic sites during development?
to choose the strongest synapses that’s required to last, in many cases, a lifetime
__ does not lead to a net weakening of synaptic drive on target cells - the remaining input is the ‘best’
Synaptic elimination
At birth, multiple axons converging at the NMJ are intermingled (inter-axonal competition). By postnatal day __ , a single axon innervates the post-synaptic site.
15
__ neural activity is a feature in early brain development
Synchronous
As development continues, patterns of neuronal firing of motoneurons changes from synchronous to asynchronous, which leads to __
inter-axonal competition and synaptic elimination
What is the irreversible competitive AChR antagonist found in snake venom?
Alpha-bungarotoxin (blocks transmission through AChR clusters, thereby blocking activity in postsynaptic cell)
What is crucial for the maintenance of synapses?
Post-synaptic activity
Does asynchronous neuronal firing develop before or after synapse elimination?
before
What is the Neurotrophic Factor Hypothesis?
Developing neurons compete with each other for a limited supply of a NTF provided by the target tissue i.e. the neuron that takes up the most BDNF, for example, survives
The pro-form of BDNF binds…
p75 (low affinity receptor)
The mature form of BDNF binds…
TrkB (high affinity tropomyosin-related kinase receptor)
True or False: The pro-form of BDNF is biologically inactive
False - it just binds a different receptor to mBDNF
What protein also forms a high affinity binding site with p75?
Sortilin
Mature neurotrophins can stimulate __
neuronal survival
Pro-neurotrophins may induce __
apoptosis
Intracellular cleavage of proneurotrophins by the action of …
furin or proconvertase
Extracellular cleavage of proneurotrophins by the action of …
matrix metalloproteinase (MMP)-7 or -9
Morpholino knock-down endogenous TrkB shows that…
mBDNF plays an active role in preventing synaptic retraction of the active terminals through TrkB
