The objective is to understand the neuronal synchronization process in the mammalian cortex. The principal issues to be examined are: (1) The membrane and synaptic processes underlying synchronization. (2) The chemical basis of synaptic transmission. (3) The plastic properties of synapses for synchronization. Our previous work primarily dealt with (1). Detailed information has been obtained on two sets of synapses directly involved in synchronization. These are, the excitatory connections between hippocampal pyramidal cells and the feedback inhibitory synapses for the pyramidal cells. Simultaneous recordings have been made from the pre- and postsynaptic cells of these synapses providing, for the first time, data on the unitary events. These results provided the background necessary for explorations into issues (2) and (3). The specific objectives of the proposal are (1) To examine the convergence and divergence of the excitatory connections. (2) To assess the role of glutamate and its agonists as a transmitter of the excitatory synapses. (3) To examine synaptic modifications that lead to neuronal synchronization following tetanic afferent stimulations. Hippocampal slices will be used to examine the physiology, pharmacology and plasticity of the synaptic process. The acutely dissociated hippocampal cells will be used to provide corraborative information on the pharmacology of receptors and properties of ionic channels activated by transmitter agents. The synchronized discharge examined here can be compared directly to the interictal spikes recorded in epilepsy. We anticipate that the results of the proposed study will provide fundamental information on the integrative properties of the hippocampus both in disease (epilepsy) and the normal state.
