Visual cortical circuits exhibit experience-dependent plasticity within well defined critical periods. A popular hypothesis is that heightened plasticity during the critical period results from enhanced activation of cortical NMDA receptors. Biophysical properties of postsynaptic NMDA receptors and of presynaptic glutamate release at cortical synapses change dramatically during the critical period. Despite spectacular advances in our understanding of the molecular mechanisms underlying many of these changes, we know remarkably little about their functional consequences for how NMDA currents summate during physiologically relevant patterns of activity. Nevertheless, it is widely believed that a major factor that determines whether or not a given pattern of presynaptic activity will cause long-term synaptic change, and the sign of that change, is the time course and amplitude of the resulting NMDA current in the postsynaptic cell. Here we propose to measure the development of six aspects of excitatory synaptic transmission that are key determinants of the dynamics of NMDA receptor activation during patterned activity: 1) presynaptic short-term synaptic plasticity and the resulting dynamics of AMPA-mediated currents, 2) the ratio of NMDA and AMPA activation at individual cortical synapses, 3) the kinetics of unitary NMDA-mediated currents, 4) voltage-dependent block of NMDA receptors by magnesium ions, 5) saturation of NMDA receptors during repetitive activation, and 6) desensitization/deactivation of NMDA receptors in response to calcium influx. Single and dual whole cell recordings in slices will be used to study the development of glutamatergic transmission mediated by AMPA and NMDA receptors in layers 2/3 and 4 of rat visual cortex. We will then manipulate this development by rearing rats under conditions of monocular and binocular deprivation. An essential goal of our studies will be to develop a comprehensive quantitative description of how these factors interact to alter the dynamics of excitatory transmission during normal and altered visual development.
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