DENDRITIC EXCITABILITY IN HIPPOCAMPUS

Baylor College Of Medicine, Houston TX

Investigators

Abstract

Epilepsy is a disease of neuronal hyperexcitability. Several models of epilepsy at the cellular level have pointed to the CA3 hippocampal pyramidal cell as a locus of epileptogenic burst firing. Recent recordings in CA1 hippocampal and neocortical pyramidal cells have shown that the dendrites of these cells are capable of firing action potentials independently of the cell soma, and that somatic action potentials are actively propagated into the dendrites where they can influence dendritic excitability. This study proposes to examine active electrogenesis in the dendrites of CA3 pyramidal cells in order to determine whether these dendrites possess active properties similar to those of CA1 pyramidal cells, and how these properties might contribute to epileptiform firing. Action potential propagation will be visualized in CA3 cells using dendritic patch clamping and imaging of intracellular calcium concentration with fluorescent dyes. These techniques should allow the localization of the initiation sites of both sodium- and calcium-dependent action potentials within the dendrites. The firing and invasion of the dendrites by somatic action potentials will also be assessed under both normal and epileptogenic conditions induced by potassium channel blockers and GABAergic disinhibition. The influence of these "backpropagating" action potentials on dendritic excitability will be studied, and the distribution and pharmacology of dendritic calcium channels will be mapped. It is hoped that these studies will provide further evidence for the role that active dendrites play in contributing to the overall behavior of the single neuron, particularly under conditions which lead to epileptiform firing.