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WORKSHOP ON:
CENTRAL PROBLEMS IN SINGLE CELL COMPUTATION
16-18 September 2002
By invitation only
Venue
B10 Seminar Room, Alexandra House, 17 Queen Square, London, WC1N 3AR
Control of synapse number and strength
in developing cortical networks |
Gina Turrigiano, Life
Sciences, Brandeis University, USA |
Experience plays an important role in the
refinement of central circuits, but the underlying plasticity mechanisms are not fully
understood. A non-Hebbian form of synaptic plasticity that scales synaptic strengths up or
down in the right direction to stabilize activity has recently been discovered in cultured
neuronal networks. We now demonstrate the existence of a similar mechanism in the intact
rodent visual cortex. During early development the frequency of miniature excitatory
postsynaptic currents (mEPSCs) onto principle neurons increased steeply. There was a
concomitant decrease in mEPSC amplitude which was prevented by dark-rearing. In addition,
as little as two days of monocular deprivation scaled up mEPSC amplitude in a layer- and
age-dependent manner. These data demonstrate that mEPSC amplitudes can be globally scaled
up or down as a function of development and sensory experience, and suggest that synaptic
scaling may play a role in the activity-dependent refinement of cortical connectivity. |
A prominent feature of developmental
plasticity is the structural rearrangement of presynaptic connectivity, during which some
presynaptic partners gain synaptic contacts while contacts from other partners are
eliminated. Despite the ubiquity of such structural rearrangements, the molecular signals
that induce them remain unknown. Calcium/calmodulin-dependent protein kinase II (CaMKII)
plays an important role in transducing correlated activity into postsynaptic changes in
synaptic strength. Here we show that CaMKII can also induce selective changes in the
number of synaptic connections between cultured visual cortical pyramidal neurons.
Expression of an activated form of CaMKII in individual postsynaptic neurons increased the
strength of paired transmission between some partners by a factor of 4, through both a
postsynaptic increase in quantal amplitude, and a presynaptic increase in the number of
synaptic contacts mediating transmission. At the same time that some presynaptic partners
gained synaptic connections, connections from other partners were eliminated, and there
was an overall reduction in synaptic density. The increase in connectivity was
activity-dependent, while the elimination was not. These data suggest that postsynaptic
activation of CaMKII by correlated pre and postsynaptic activity will induce presynaptic
changes in connectivity that favor active inputs. |
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