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Gatsby Computational Neuroscience Unit
Alexandra House, 17 Queen Square, LONDON, WC1N 3AR, UK
Tel: +44 (0) 20 7679 1176, Fax +44 (0) 20 7679 1173,,


annual report
the greater gatsby



16-18 September 2002
By invitation only

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.