Ih-Dependent Regulation of Intrinsic Excitability in CA1 Pyramidal Neurons

CA1 锥体神经元内在兴奋性的 Ih 依赖性调节

• 批准号: 8079008
• 负责人: Kelly Ann Dougherty
• 金额: $ 4.84万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8079008
• 关键词: Cations; Cells; Data; Exhibits; Failure; Functional disorder; Goals; Health; Hippocampus (Brain); Homeostasis; Ion Channel; Knock-out; Knockout Mice; Learning; Light; Link; Long-Term Depression; Long-Term Potentiation; Measurement; Measures; Mediating; Mediator of activation protein; Memory; Methods; Molecular; Neurons; Physiological; Plastics; Probability; Process; Property; Protein Isoforms; Protocols documentation; Regulation; Reporting; Role; Signaling Protein; Structural Protein; Synaptic plasticity; Temporal Lobe Epilepsy; Work; base; cyclopiazonic acid; density; design; hippocampal pyramidal neuron; public health relevance; research study; stem; tool; voltage; voltage clamp

DESCRIPTION (provided by applicant): This proposal is designed to investigate the relationship between the hyperpolarization-activated cation current (Ih) and intrinsic excitability (IE) of CA1 pyramidal neurons. Previous work demonstrated enhanced or reduced IE following the induction of long-term depression (LTD) and long-term potentiation (LTP), respectively, and several physiological studies have implicated Ih as the most likely mediator of IE plasticity (Fan et al., 2005; Brager and Johnston, 2007; Narayanan and Johnston, 2007). However, all evidence describing the plasticity of Ihmediated IE comes from indirect measurements of Ih using the whole cell current-clamp method. The mechanism underlying this phenomenon therefore remains unclear, and represents a substantial gap in our understanding of the regulation of IE in these neurons. This proposal investigates the biophysical mechanism of IE plasticity directly, using voltage-clamp methods capable of determining the biophysical properties of single h-channels (the ion channels responsible for Ih) as the primary tool. Specifically, the reduction in IE following LTP and the increase in IE following LTD will be investigated. This work will represent a substantial contribution to our understanding of IE homeostasis in CA1 pyramidal neurons. PUBLIC HEALTH RELEVANCE: Several recent reports have demonstrated a link between temporal lobe epilepsy (TLE) and Ih in CA1 pyramidal neurons (Shin et al., 2008; Jung et al., 2007). Ih functions as an activity-dependent regulator of intrinsic excitability (IE) in these neurons, and the observed pathophysiology associated with TLE likely stems from a failure of Ih-mediated IE homeostasis. This proposal is designed to directly investigate the currently unknown biophysical mechanism for Ih-mediated IE homeostasis, and will help to shed light on the pathophysiology of the acquired Ih-channelopathy associated with TLE.

描述（由申请人提供）：