Sensory experience plays an important role in refining the connectivity of primary visual cortex, but the identity of the synaptic plasticity mechanisms that contribute to this refinement are still under debate. Most research has concentrated on the role of correlation-based plasticity mechanisms such as LTP and LTD, but these mechanisms are highly destabilizing and are unlikely to be sufficient to explain all of activity-dependent development. Using cultured cortical networks we identified a novel form of homeostatic synaptic plasticity that scales excitatory and inhibitory synaptic strengths up and down in the correct direction to stabilize the activity of cortical networks, and more recently we have demonstrated a similar phenomenon in vivo. Here we propose to examine the role of this homeostatic synaptic scaling in experience-dependent plasticity in vivo using a classic sensory deprivation paradigm, monocular deprivation (MD) and binocular deprivation (BD) using lid suture. MD and BD have been used extensively to study activity-dependent plasticity, but the effects of these manipulations on intracortical circuitry have never been probed in detail. We will approach this problem by manipulating activity in rodent visual cortex through MD and DR, then cutting slices of primary visual cortex and obtaining whole-cell recordings to measure quantal currents and paired synaptic transmission. We will ask whether the quantal currents for excitatory and inhibitory synapses are scaled in the opposite direction in response to altered visual input, whether this scaling displays critical periods as do other forms of activity-dependent plasticity, and whether the rules for synaptic scaling are specific for particular classes of excitatory and inhibitory inputs. These experiments will lay an important foundation for understanding the detailed changes in cortical circuitry that arise as a result of altered sensory experience, and will have important implications for the mechanisms of visual abnormalities such as amblyopia.
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