NEURONAL FUNCTION IN CEREBELLO-MOTOR AND THALAMOCORTICAL INTERACTION

项目I的目标是将动态神经网络特性与 其组成神经元的内在电活动。 的 该项目将涉及三个方面：A）电压依赖性离子电流 体外浦肯野细胞及其在神经元整合中的作用。 这些 将在宏观和单通道电流水平下进行研究， 全细胞和细胞贴附膜片钳技术，并将关注 INa（P）和伊卡。 该研究还将离子电流与 所涉及通道的分子生物学特征， 最终的目标是基因敲除和钙浓度成像， 解决“复杂钙微区”的问题。“这部分的 将与希尔曼博士合作开展工作。 数学模型 浦肯野细胞活性的变化将作为一种启发式工具来评估单个 钙泵的通道和宏观现状和问题 和通过成像结果确定的IP3活性。 B）功能 小脑脑干的组织及其与运动的关系 控制 在体外细胞培养中在单细胞水平进行的实验 下橄榄切片将确定，电生理学和手段 钙成像，离子基础和通道分布负责 for neuronal神经振荡. 下橄榄摆动与 小脑核回流对电耦合调节 抑制，并涉及关于产生的体内范例， 触须系统的运动。 这项研究将涉及多个浦肯野 细胞记录及其与自发性和皮质性的时间关系 引起触须运动。 该范例将涉及离子电流和 它们对运动执行的药理学性质， 橄榄小脑系统 C）40 Hz振荡的离子基础， 单个丘脑神经元钙振荡的神经肽调节 及其与丘脑和丘脑皮质折返的关系 振荡和功能。 研究将包括多电极 记录在丘脑和皮层水平，在隔离豚鼠 大脑在体外。 这些实验将由计算机建模来补充 作为网络属性的预测器。

The goal of Project I is to relate dynamic neuronal network properties to the intrinsic electrical activity of their constitutive neurons. The project will address three areas: A) The voltage-dependent ionic currents in in vitro Purkinje cells and their role in neuronal integration. These will be studied at macroscopic and single-channel current level using whole-cell and cell-attached patch clamp techniques and will concern INa(P) and ICa. The study will correlate in addition ionic currents to the molecular biological characteristics of the channels involved, with the ultimate aim at gene knockout and at calcium-concentration imaging to address the issue of "complex calcium microdomains." This part of the work will be done in collaboration with Dr. Hillman. A mathematical model of Purkinje cell activity will serve as a heuristic tool to assess single channel and macroscopic current results and issues concerning calcium pump and IP3 activity as determined by the imaging results. B) Functional organization of the cerebellar brain stem and its relation to motor control. Experiments performed at the single-cell level in the in vitro inferior olive slice will determine, electrophysiologically and by means of calcium imaging, the ionic basis and channel distribution responsible for neuronal oscillation. Inferior olive oscillation will be related to the regulation of electrical coupling by cerebellar nuclear return inhibition, and to an in vivo paradigm concerning the generation of movement in the vibrissal system. The study will entail multiple Purkinje cell recording and their temporal relation to spontaneous and cortically evoked vibrissal movement. The paradigm will relate ionic currents and their pharmacological properties to movement execution as modulated by the olivocerebellar system. C) The ionic basis for 40-Hz oscillation and neuropeptide modulation of calcium oscillation in single thalamic neurons and its relation to thalamothalamic and thalamocortical re-entrant oscillation and function. The studies will include multiple electrode recordings at the thalamic and cortical levels, in the isolated guinea pig brain in vitro. The experiments will be complemented by computer modeling as a predictor of network properties.