Modulation of CA1 Neuronal Excitability by SK Channels.

SK 通道对 CA1 神经元兴奋性的调节。

• 批准号: 6550285
• 负责人: AARON C GERLACH
• 金额: $ 2.94万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-09 至 2003-04-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6550285
• 关键词: action potentials; biological signal transduction; calcium; electrophysiology; gene targeting; genetically modified animals; glutamate receptor; hippocampus; laboratory mouse; neural conduction; neurons; neurophysiology; postdoctoral investigator; potassium channel; synapses; voltage /patch clamp

DESCRIPTION (provided by applicant): Neuronal excitability requires the summation of post-synaptic potentials to attain threshold for the propagation of a burst of action potentials. In CA1 hippocampal pyramidal neurons, small conductance Ca2+-activated K+ (SK) channels are believed to underlie the two Ca2+-dependent components of the afterhyperpolarization (AHP). These SK channels can be activated synaptically suggesting that they may contribue to excitatory post-synaptic potentials (EPSPs). By modulating both the magnitude and duration of EPSPs, SK channel activity may determine whether a post-synaptic CA1 neuron reaches threshold for action potential propagation. By modulating action potential bursting patterns and EPSPs, these channels potentially contribute to the most fundamental role of CA1 neurons in physiology: the integration of learning and memory. Consistent with this proposal is the observation that pharmacological modulation of SK channels in vivo stimulates hippocampal-dependent learning in mice. Three distinct SK channel subunits, SK1, SK2 and SK3, have been cloned and all are expressed in CA1 neurons. Because of the potential neurophysiologcal importance of these channels, the overall aim of this proposal is to investigate the physiological contribution of these different SK channel subunits to the AHP, spike frequency adaptation, and EPSPs of CA1 neurons. To test, I will investigate SK transgenic mice in which SK expression is regulated acutely and post-developmentally in a tissue specific manner.

描述(由申请人提供)：神经元的兴奋性要求突触后电位的总和达到动作电位突发传播的阈值。在CA1区的海马锥体神经元中，小电导的钙激活K+(SK)通道被认为是后超极化(AHP)的两个钙依赖成分的基础。这些SK通道可被突触激活，提示它们可能参与兴奋性突触后电位(EPSP)。通过调节EPSP的幅度和时长，SK通道的活动可能决定突触后CA1神经元是否达到动作电位传播的阈值。通过调节动作电位爆发模式和EPSP，这些通道可能有助于CA1神经元在生理学中最基本的作用：学习和记忆的整合。与这一建议一致的是，观察到体内SK通道的药理调节刺激了小鼠的海马区依赖学习。3个不同的SK通道亚基SK1、SK2和SK3已经被克隆，并且都在CA1神经元中表达。鉴于这些通道的潜在神经生理学重要性，本研究的总体目标是研究这些不同的SK通道亚单位对CA1神经元的AHP、峰频率适应和EPSP的生理贡献。为了进行测试，我将研究SK转基因小鼠，在这些小鼠中，SK的表达以组织特异性的方式在发育后期受到尖锐的调控。