There is compelling evidence for the involvement of the hippocampal formation in the processing and storage of information by the nervous system. Furthermore, these functions must be accomplished by the basic units of the nervous system, the neurons, along with their various synaptic interconnections. Individual pyramidal neurons in the hippocampus and entorhinal cortex are complex units of integration that dynamically change with their environment. Our 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 upon its dendritic tree. 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 properties, function, and plasticity of voltage-gated ion channels expressed in pyramidal neuron dendrites in hippocampus and entorhinal cortex. During the previous funding period we investigated certain types of potassium, sodium, and inward rectifier (h) channels in dendrites of these neurons and their plasticity under several different conditions. In this renewal application we propose to continue our investigation of dendritic ion channel plasticity by focusing on the bi-directional changes in several ion channels that are highly expressed in pyramidal neuron dendrites and that occur in parallel with long-term potentiation and long-term depression. These channels are responsible for the h current, a transient outward potassium (A) current, and a persistent sodium current. We will be addressing the physiological and biochemical mechanisms underlying the plasticity of these channels and the role they play in the plasticity of intrinsic excitability of these neurons. The experiments will utilize hippocampal brain slices, dendritic patch-clamp electrophysiology, and high-speed fluorescence imaging of Ca2+ and membrane potential.
Neuronal dendrites, and the ionic channels expressed in them, are altered in specific ways in epilepsy, Alzheimer's disease, schizophrenia, and many other neurological and psychiatric disorders. We expect that the results of our studies will provide important information about the functional significance of these disease-related changes in dendrites.
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