There is compelling evidence for the involvement of the hippocampus in the processing and storage of information by the nervous system. Furthermore, these functions must be accomplished by the basic units of the hippocampus, the neurons and their various interconnections. Individual pyramidal neurons in the hippocampus are complex units of integration that dynamically change with their environment. The long-term objective is to understand how a pyramidal neuron integrates and stores the information it receives from the tens of thousands of excitatory and inhibitory synaptic inputs impinging on its dendrites. Understanding how a pyramidal neuron performs these functions will only come from knowledge about the biophysical properties of these neurons and how they respond to synaptic input. This project focuses on the properties and function of voltage-gated ion channels in pyramidal neuron dendrites. Previously, single Na+ channels and at least three types of Ca2+ channels in dendrites of CA1 neurons were investigated. Here, it is proposed to continue the investigation of dendritic ion channels by focusing on certain unknown properties of these channels, on exploring further the properties of newly discovered channels, and on the neurotransmitter modulation of these channels. The experiments will utilize hippocampal brain slices, patch-clamp electrophysiology, computer modeling, and two recent techniques: high-speed fluorescence imaging and dendritic patch clamping under visual control. Neuronal dendrites are altered in specific ways in epilepsy, Alzheimer's disease, and schizophrenia. It is expected that the results of the study will provide important information about the functional significance of these disease-related changes.
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