DEVELOPMENT&MODULATION OF CALCIUM CURRENTS IN NEOCORTEX

描述：(申请人摘要) 新皮质锥体神经元是研究这一机制的模型系统 以及突触输入转导到棘波序列的意义。几个 这种转导过程的某些方面是依赖于钙离子的，包括调节 峰间期(ISI)、峰频率适应(SFA)、峰电位 定时和后超极化(AHP)。锥体细胞至少表达 五种不同的高压激活的钙通道。我们假设钙离子 进入对这些细胞有不同的后果，取决于哪种钙 涉及通道子类型。这种功能划分的一个例子是 AHP的产生：N型、P型和Q型通道耦合到SAHP和P型 致mAHP。控制钙离子进入的两个关键负反馈系统是 钙依赖的钙通道失活和钙依赖的激活 K+通道。这两个过程都是锥体细胞放电的潜在调节器 行为。我们将使用全细胞电记录和Fura-2钙成像 急性分离和脑内成熟锥体细胞的培养技术 测试有关钙依赖作用的假说的切片准备 失活及其与动作电位、[Ca~(2+)]i和AHP的关系 电流(由于钙依赖的K+通道)。目标1解决了以下问题的重要性 钙离子依赖的钙通道亚型及哪些通道亚型失活 都牵涉其中。目标2描述了发射频率和发射频率之间的关系 成熟锥体细胞内的IAHP和[Ca~(2+)]i。这些数据对于 了解锥体细胞如何整合突触输入，以及如何 过程受传递体和个体发育的影响。(在新皮质锥体 神经元，钙离子和钙-钾通道都是发育调节的，并 是几种神经调节剂的靶标)。神经元的活动及其调节 调节皮质功能和皮质的使用依赖性可塑性 关系。这些研究将有助于理解必要的皮质 注意力、学习和记忆等功能以及基本机制 如癫痫、焦虑和抑郁等疾病。

DESCRIPTION: (Applicant's Abstract) Neocortical pyramidal neurons are a model system for study of the mechanisms and significance of transduction of synaptic inputs into spike trains. Several aspects of this transduction process are Ca2+-dependent, including regulation of the interspike interval (ISI), spike frequency adaptation (SFA), spike timing and afterhyperpolarizations (AHPs). Pyramidal cells express at least five different high voltage-activated Ca2+ channels. We hypothesize that Ca2+ entry has different consequences for these cells, depending upon which calcium channel subtypes are involved. An example of such partitioning of function is generation of AHPs: N-, P-, and Q-type channels couple to the sAHP and P-type to the mAHP. Two critical negative feedback systems controlling Ca2+ entry are Ca2+-dependent inactivation of Ca2+ channels and activation of Ca2+-dependent K+ channels. Both processes are potential regulators of pyramidal cell firing behavior. We will use whole cell electrical recordings and fura-2 Ca2+ imaging techniques on mature pyramidal cells in both acutely dissociated and brain slice preparations to test hypotheses about the roles of Ca2+-dependent inactivation and the relationships between action potentials, [Ca2+]i, and AHP currents (due to Ca2+-dependent K+ channels). Aim 1 addresses the importance of Ca2+-dependent inactivation of Ca2+ channel subtypes and which channel subtypes are involved. Aim 2 characterizes the relationships between firing frequency, IAHP, and [Ca2+]i in mature pyramidal cells. These data are important for understanding how pyramidal cells integrate synaptic inputs, and how this process is influenced by transmitters and ontogeny. (In neocortical pyramidal neurons, both Ca2+ and Ca2+-dep K+ channels are developmentally regulated and are targets for several neuromodulators). Neuronal activity and its modulation regulate cortical function and the use-dependent plasticity of cortical connections. These studies will contribute to understanding essential cortical functions such as attention, learning, and memory as well as basic mechanisms of diseases such as epilepsy, anxiety and depression.