A combined morphological and electrophysiological study of adult and developing Macaca nemestrina visual cortex is planned. The developmental anatomy of thalamic input layer 4 will be studied: a) by EM quantitative analysis of synaptic distribution in layers 4A, 4Ca and 4Cb during the first 12 postnatal weeks compared to the adult. This study will utilize labeled thalamic and cortical synapses to determine possible differences in developmental rates of extrinsic vs intrinsic pathways: b) determining the developmental sequence within layer 4 in which the calcium-binding protein, parvalbumin (PV), voltage-gated calcium channels, and NMDA glutamate receptors appear. Ligand binding, light and EM immunocytochemistry will be used to detect these markers of functional maturity in layer 4 neurons. The electrophysiology of adult and infant cortex will be studied using in vitro cortex slices from rat and monkey. Extracellular recording will be used to obtain the transmembrane voltage response to intracellularly and synaptically evoked currents in order to describe the electrophysiological properties of identified neurons through development. The same neurons will then be filled intracellularly with biocytin so that their morphology can be determined. Double label immunocytochemistry will then be applied to correlate electrophysiology with the presence or absence of PV. The functional role of intracellular calcium buffers in neurons of adult cortex will be tested by injecting PV into neurons which do not normally contain it, and by injecting calcium chelators into both PV+ and PV-neurons. These correlated approaches will provide important new anatomical and functional information on intrinsic and extrinsic pathway circuits in monkey layer 4 and relevant biophysical information, now totally lacking, on how these circuits develop during the most critical period for layer 4 development. This new information may provide much needed insight into what goes wrong when visual input is abnormal or deprived during this period.
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