Our long-term goal is to understand the membrane and synaptic mechanisms responsible for epileptiform activity in the hippocampus. During the previous funding period, our efforts focused on the investigation of the biophysical properties of CA3 pyramidal neurons and mossy fiber (MF) synapses. The CA3 subfield of the hippocampus is particularly vulnerable to the development of epileptiform activity. We propose to continue our investigation of neurons and synapses in CA3 but expand our focus to include recurrent excitatory synapses, the synapses responsible for the paroxysmal depolarizing shift in this region. We will use electrophysiological techniques in conjunction with the rat hippocampal properties of recurrent excitatory synapses, (2) the role of long-term potentiation of recurrent and MF synapses in the initiation and maintenance of epileptiform activity, and (3) the functional consequences of the aberrant growth of MF synapses in kindled animals. These studies will provide much needed information about the recurrent excitatory synapses (and the MFs that so easily engage them) and the contribution by these synapses to epileptogenesis in this area of the brain.
