Synapse Elimination

1
Synapse Elimination
during development, more synapses are formed than
survive myotubes are transiently innervated by
more than 1 motor neuron only 1 ennervates
adult fibers lateral geniculate nucleus receives
20 inputs from retina in development only 1 or
2 survive the first month individual synapses do
not survive overall strength does not
decrease each axon connection becomes 50x
stronger, probably through many connections as
well as stronger individual connections
2
Synapse Elimination
in the submandibular ganglion, the number of
synapses double when the number of incoming
axons decreases 5-fold synapse elimination
occurs after most cell death but the cells that
lose their connections survive sharpens
specificity by making connections all or
nothing total extent of synapse elimination is
difficult to measure in CNS may also be due to
equivalent pools of cells competing for
equal postsynaptic cells
3
Synapse Elimination
insects and lower vertebrates have many fewer
redundant neurons and a lot less synaptic
elimination neuromuscular junctions are easy to
observe using labeled axons and synaptic
components (ie. bungarotoxin that binds to
nAChRs) when 2 axons compete at the same
neuromuscular junction, one axon retracts as
the other takes over the synaptic
site decision is highly dynamic other synapses
the axon withdraws and the AChR cluster
slowly disperses without activity
4
Synapse Elimination
competition takes place indivdiually between
presynaptic neurons for postsynaptic
space transgenic mice with 2 labels show all
synapse competitions between the same 2
neurons have the same result competition between
2 different neurons can have different
results size of axon terminals generally
reflect the likelyhood of survival
5
Synapse Elimination
activity appears essential for synaptic
elimination Hebbian synapses active synapses
become stronger while inactive connections are
lost-- summarized as 'use it or lose
it' suggests 2 signals one to stabilize a given
synapse second to
destabilize inactive synapses calcium appears
to be one (or both) of these signals synaptic
refinement seems to require asymmetric firing of
2 synapses
6
Visual Cortex Development
visual cortex receives input from both eyes via
an intermediate connection through the lateral
geniculate nucleus initially, layer IV cells are
driven by inputs from both eyes later, same
cells are driven only by 1 eye-- some connections
are lost forms occular dominance columns--
'stripes' of monocular connections
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Visual Cortex Development
synaptic arbors get refined, but get stronger on
the connected cells overlaps are selectively
removed critical period time during which
connections are plastic afterwards they
cannot be changed by changed activity
patterns if activity is blocked in one eye
that eye's columns are smaller if blocked in
both eyes, columns never form if activity is
blocked in the cortex columns never
form after some period, activity changes do
not change columns
8
Visual Cortex Development
GABA activity in the cortex seems to play a role
in rodent monocular development critical
periods there can be activated by benzodiazapines
which increase the strength of GABAergic
synapses partial activity also allows only
partial refinement of connections synaptic
homeostasis suggests each cell receives some
constant level of input, either lots of weak
or fewer strong connections if too strong,
inhibitory connections reduce the neuron's
activity
9
Thalamus Lateral Geniculus Refinement
retinal connections to the LGN also refine--
layers instead of columns refinement includes
new layer-specific connections and retractions
occurs before birth, suggesting retinal calcium
waves are important
10
Cerebellar Purkinje Cells
climbing fibers from the 'inferior olive nucleus'
synapse on Purkinje cells one Purkinje cell
receives synapses from many climbing fibers
early but mature cells synapse with 1 climbing
fiber having many synapses granule cell input to
Purkinje cells are required to refine this
connection blockade of NMDA receptors also block
climbing fiber refinement