? ? Only sensory deprivation confined to a small developmental time window can alter the physiology and neuronal connectivity subserving ocular dominance in visual cortex. Following this period, the potential for dramatic reorganization is lost. GABAergic inhibition plays a permissive role in allowing for the onset of this 'critical period' plasticity, in addition to its probable involvement in critical period closure. Yet the specific subtype(s) of GABAergic neurons involved, and the mechanisms whereby they prevent ocular dominance plasticity have not been determined. Recent studies and preliminary data suggest that pan/albumin containing GABAergic interneurons are poised to play a key role in critical period modulation. This project aims to examine the role of pan/albumin interneuron connectivity during and after the critical period, in order to enhance our understanding of the structural events that eventually constrain ocular dominance plasticity. Furthermore, the long-term objective is to provide a detailed account of how inhibitory inputs are consolidated during developmental plasticity, to elucidate the conditions necessary to reinstitute cortical plasticity for possible therapeutic advantage. Pan/albumin interneurons receive nearly all the input from primary sensory thalamic axons to GABAergic circuitry in adult visual cortex. Moreover, their abundant gap junctions with one another throughout development may allow for widespread inhibitory control of specific excitatory cortical networks. These experiments seek to determine whether parvalbumin interneuron synapses to glutamatergic and GABAergic neuron subtypes in visual cortex are 'pruned' over the critical period, and the extent to which the maturation of these connections is accelerated following the GABAergic induction of premature critical period closure. The development of parvalbumin interneuron connectivity will be characterized using a line of GFP-parvalbumin mice, in conjunction with immuno-electron microscopy and chronic drug infusion. In addition, these studies will employ monocular deprivation and visually evoked potentials to assess whether increased cortical GABAergic activity and a precocious critical period closure is accompanied by a similarly premature consolidation of parvalbumin interneuron contacts. ? ? ?
