The thalamocortical synapse is the sole gateway for all sensory information entering the neocortex. It is therefore a crucial linchpin in the pathways that lead from sensation to sensory perception, and its normal development is a necessary prerequisite for acquisition of mature cortiCal function. A unique in vitro preparation in which the thalamocortical pathway is retained and functional will be utilized in conjunction with whole-cell recordings, intracellular staining, axonal tracing and confocal imaging, to study morphological, pharmacological and physiological development of thalamocortical synapses from their genesis in the early neonatal period to maturity. The proposed study will examine in detail changes in the properties of the synapse, with particular emphasis on the NMDA receptor-mediated component which is thought to endow the system with the capacity to adjust to environmental influences. Whole- cell recordings from cortical cells will address several specific questions: (1) Are thalamocortical inputs to cells in the deep layers (layers V/VI) formed non-specifically and in exuberance in the early neonatal period, and """"""""inappropriate"""""""" connections later retracted? (2) Do deep layer cells receive the majority of their synaptic inputs on their basal dendrites, from thalamocortical terminals in the deep layers, or on their apical dendrites, from thalamocortical terminals in layer IV? (3) Is there a developmental reduction in the relative contribution of NMDA vs non-NMDA receptor-mediated synaptic currents, in the activation time of the NMDA receptor-mediated current, in its Mg sensitivity or in its Ca permeability, which could account for loss of plasticity in the mature animal? Dual simultaneous recordings from synaptically coupled thalamocortical projection cells and cortical layer IV cells will address development of thalamocortical synaptic function at the single axon level and will examine integrative properties of the thalamocortical synapse. Quantal analysis methods will reveal whether the developmental increase in terminal arbor complexity is accompanied with increased divergence or with an increase in the size of the unitary response, and whether the latter increase is post- or presynaptic in origin.
