HTHSCI 1DT3 Study Guide - Midterm Guide: Point Mutation, Morris Water Navigation Task, Bulgarian State Railways
23 Jun 2018
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Describe the mechanisms of synaptogenesis and the role of synaptic plasticity in brain functions
Explain the variability in synaptic transmission and the role of activity-induced synaptic plasticity in
development, learning and memory with reference to specific examples.
Introduction
Synapse definition – specialised junction between two neurons, allows transmission of
impulses between nerves and forms complex circuitry by which signals can be modulated.
Electrical vs. chemical synapse. Electrical synapse – small gap junctions, direct flow of ions
from one neuron to another. FAST conductance of signals).
Chemical synapse – Slower, involve release of neurotransmitter. Action potential reaches
presynaptic knob and causes depolarisation (influx of Na+), leads to opening of voltage
gated Ca2+ channels. Ca2+ influx causes movement of docked vesicles in presynaptic knob
(containing NT) to move towards presynaptic membrane – fusion of vesicle releases NT
into synaptic cleft. NT binding to postsynaptic receptor results in signalling in postsynaptic
neuron.
Synaptic Transmission
Synapses can be excitatory (Glu, gly NT) or inhibitory (GABA NT) based on effect NT has
on postsynapse. (Glu – depolarisation due to Na+ influx, GABA – hyperpolarisation due to
Cl- influx)
Positioning of synaptic junctions also relevant:
Axodendritic (dendritic spines, usually excitatory)
Axoaxonic (usually inhibitory)
Axosomatic (modulatory)
Kiss and Run Theory – suggested by Gandhi (2003) wherein Ca2+ influx into presynapse
may not always stimulate vesicle fusion, and allows for variability in synaptic transmission.
Synaptogenesis
Generally rapid process – mostly occurs postnatally.
Occurs throughout life and important in developing new memories.
Synaptogenesis during neuronal development occurs through axonal growth and guidance
of growth cones (which form presynapses when their target is reached).
Axonal growth occurs through key inductive cues (long range/short range,
positive/negative cues)
Believed that pre- and post-synaptic events occur even before meeting each other (i.e.
become specialised before they meet their partner).
Idea that synapses can form completely without any neuronal activity (i.e. purely based on
growth factors and axonal guidance cues). However, after synapses have formed – need to
have activity during critical period or synapses are remodelled/lost (use it or lose it).
Neurexin and neuroligin – neuroligin expressed on postsynaptic membrane binds to
neurexin (expressed on growth cone). Binding stimulates conversion of growth cone into
presynapse.
Wnt stimulates presynaptic differentiation – modulation of MT dynamics in growth cone.
Surrounding glia are important for forming synapses (Mauch 2001) - Retinal ganglion cells
in eye forms more synapses in vitro if on a layer of astrocytes (due to increased cholesterol)
Adhesion molecules (cadherins, integrins, ephrins and neurexin) hold neurons together at
synapse by acting as a scaffold.
N-Cadherin shown to promote spine stability (Mendez 2010) – delta 390 mutation
experiment mutated N-Cad, and lacked ECM causing difficulty creating synapses.
Actin cytoskeleton
Important for remodelling and synaptic plasticity – impact on learning and
memory.
Actin filaments also important for stabilising and maintaining synapse function in
both presynapse (controls RESERVE POOL of synaptic vesicles, and docking of
READY-RELEASABLE POOL).
In postsynaptic membrane, actin meshwork hold protein and receptors in place and
control shape of spine.
Synaptic strength (and degree of plasticity?) associated with degree of actin
polymerisation in dendritic spines (postsynaptic membrane) influenced by Arp
complex.
Glial wrapping – thought to stabilise and make synaptic junctions permanent. Astrocytes
thought to regulate synaptic environment (e.g. ions K+, and neurotransmitters). (Barres
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