The general objective of this research proposal is to establish the role that voltage-gated ion channels located within dendritic arborizations have in determining the fundamental functions of neurons. A first step towards this objective is to establish exactly which types of voltage- gated ion channels are present in neuronal dendrites. This project will characterize the properties and distribution of dendritic voltage-gated K+ and hyperpolarization-activated (Ih) channels. Furthermore, the role that one of these channel populations (Ih channels) has in determining the basic electrical properties of CA1 dendrites will be directly investigated. Single K+ and Ih channel activity will be recorded directly from the dendrites of hippocampal CA1 pyramidal neurons in order to rigorously describe their biophysical and pharmacological properties. Simultaneous dendritic and somatic whole-cell recordings will be used to investigate dendritic ih channel function. The information attained from these studies will vastly improve our understanding of the physiological signals that are generated in and propagate through neuronal dendrites. Furthermore, a more complete understanding of neuronal membrane excitability will aid in determining the basic mechanisms of such neuronal diseases as epilepsy, alzheimers disease and neurogenic hypertension.

R29NS035865

1996-12-01

2001-11-30