It is likely that enhanced transmission at excitatory synapses contributes to the hyperexcitability of the epileptic brain. This project will address this possibility by characterizing excitatory synaptic transmission in kindled animals. The experiments will examine synaptic transmission in the hippocampus, a region of the brain particularly susceptible to seizures, and will focus on th excitatory synapses of CA3 pyramidal neurons, neurons that are prone to hyperexcitability and ra an essential part of the hippocampal trisynaptic circuitry. The two synapses we will examine are the """"""""mossy fiber"""""""" synapse between dentate granule neurons and CA3 neurons and the associational-commisural synapse between CA3 neurons. We first will test the hypothesis that excitatory synaptic transmission is enhanced by kindling by comparing the properties of unitary postsynaptic currents (EPSCs) evoked at these synapses in normal and kindled animals. We next will test the hypothesis that kindling enhances the component of synaptic transmission mediated by NMDA-type glutamate receptors by examining the pharmacological properties of EPSCs and the spatial distribution of postsynaptic glutamate responses. Finally, we will determine whether kindling changes synaptic transmission via modification of postsynaptic glutamate receptors by performing a quantal analysis of EPSCs. This analysis will define the postsynaptic and presynaptic contributions to any kindling-induced changes in synaptic transmission. The locus of any presynaptic component will be determined by measuring Ca signals in the mossy fiber terminals and by examining the functional roles of proteins potentially important for transmitter release.
Showing the most recent 10 out of 219 publications
