NEURONAL FUNCTION IN CEREBELLO-MOTOR AND THALAMOCORTICAL INTERACTION

项目I的目标是将动态神经网络属性与 它们构成神经元的内在电活动。这个 该项目将涉及三个领域：a)电压相关离子流 体外培养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上使用 全细胞和细胞附着式膜片钳技术 INA(P)和ICA。除了离子流外，这项研究还将与 所涉及的通道的分子生物学特征， 基因敲除和钙浓度成像的最终目标是 解决“复合钙微域”的问题。这一部分是 这项工作将与希尔曼博士合作完成。一种数学模型 浦肯野细胞活性将作为一个启发式工具来评估单个 渠道和宏观方面的成果和钙泵存在的问题 以及由成像结果确定的IP3活性。B)功能 小脑脑干的组织及其与运动的关系 控制力。在体外单细胞水平进行的实验 下橄榄切片将通过电生理和方法确定 对钙离子成像，离子基础和通道分布负责 用于神经元振荡。劣质橄榄振荡将与 小脑核回对电耦合的调节 抑制，以及关于产生 振动系统中的运动。这项研究将涉及多个浦肯野 细胞记录及其与自发和皮质的时间关系 引起振动的运动。该范例将把离子流和 它们对动作执行的药理作用受 橄榄小脑系统。C)40赫兹振荡的离子基础和 神经肽对单个丘脑神经元钙振荡的调节作用 及其与丘脑和丘脑皮质折返性折返的关系 振荡和功能。研究将包括多个电极 离体豚鼠丘脑和皮质水平的记录 大脑的体外培养。这些实验将得到计算机模拟的补充 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.