There is substantial evidence to suggest that the membrane properties of individual cortical neurons are functionally as important in determining the overall behavior of cortical circuits as are the attributes of the interconnections between cells. This conclusion seems valid not only in the context of normal cortical functioning but, also, in certain pathological conditions as well. In some epileptic disorders, for example, in which there is abnormal electrical activity in the cortex, epileptic discharges occur not only in single cells, but, also, sychronously in synaptically connected groups of neurons. The initiation and the spread of activity are apparently determined by a combination of the endogenous membrane properties of individual cells and the specific interactions among the various neuronal components of the circuitry. The goal of the research outlined in this proposal is: (1) to isolate, from defined circuits in rat primary visual cortex, neurons with identified connections and known developmental fates; and (2) to characterize the ionic currents (and transmitter related properties) of these cells. The long range goal of the work is to provide an understanding of the mechanisms controlling bursting activity in identified (single) cells and the sychronized firing of population cells (including identified cells) within defined cortical circuits. Using the whole-cell patch-clamp recording method, we shall study the electrophysiological properties of single corpus callosum projecting, geniculate projecting and intrinsic cortical neurons in dissociated cell culture. These cell types will be identified following postnatal, intracerebral injections and retrograde axonal transport of fluorescent markers. In the initial experiments, particular emphasis will be placed on characterizations and comparisons of voltage-activated currents. Later experiments will focus on the postsynaptic effects of the inhibitory neurotransmitter, GABA, on identified cells. GAD immunocytochemistry will be employed to determine the GABAergic nature of identified neurons and to verify the presence of GABAergic terminals on retrogradely labelled cortical cells in culture.
