EXPERIMENTAL STUDIES OF SENSORY PATHWAYS

所提出的工作旨在扩展单个神经元的高分辨率 应用解剖学和免疫细胞化学相结合的技术分析 更精确地描述细胞、电膜和离子 电流；神经递质和神经调节器作用；以及 基底节内的神经元成分。而且，与此同时， 拟议的工作旨在对各种 基底节的核功能比常规方法所能获得的 单个或多个单元记录或通过传统的解剖学技术。 感兴趣的区域将通过密集使用油井来解决 在我们实验室建立的方法学，即细胞内记录 而用生物细胞素和其他标记材料进行细胞内标记是 结合随后的光学和电子显微镜分析。在……里面 此外，组织化学方法，包括逆行和顺行 运输技术，将被采用。 这一融合的多学科分析将定向到体外 切片制备与培养和急性分离神经元制备 取自大鼠新纹状体苍白球内足底核， 黑质、丘脑下部与三组AIMS： 第一组将表征膜的性质(包括离子 K、Na、Ca等电导率)通过使用神经细胞 急性分离培养的全细胞(电压)钳技术 神经元或细胞内电流钳记录在薄片上 准备工作。 第二组将描述假定的神经递质或 通过监测神经调节剂产生的离子电导的变化 药物或其激动剂和拮抗剂。待研究的发射机 多巴胺(DA)、谷氨酸和乙酰胆碱(ACh)是主要的 已知的神经递质和调节剂参与这些核操作。 我们将鉴定传递体和形态表型。 用解剖学技术研究神经元的联合技术 免疫细胞化学。 第三组是重新检查其中涉及的功能电路 核团(如下丘脑-苍白球、黑质纹状体等)通过 触发平均化技术与来自 投射及其靶神经元。 胆碱能、多巴胺能、谷氨酸能和GABA能的不平衡 基底节的系统被认为参与了病理生理学。 基底节疾病。寻找更具体的治疗方法将是 通过更清楚地了解基本的 神经节解剖学、生理学、药理学和随后的神经节失衡 金字塔外手术。

The proposed work aims to extend the high resolution of single neuron analysis with combined anatomical and immunocytochemical techniques for a more precise description of cellular, electrical membrane and ionic currents; neurotransmitter and neuromodulator action; and circuits of neuronal elements in the basal ganglia. Moreover, at the same time, the proposed work aims to provide a more meaningful interpretation of various nuclear functions of the basal ganglia than can be obtained by conventional single or multiple unit recording or by conventional anatomical technique. The areas of interest will be addressed with intensive usage of the well established methodology in our laboratory, whereby, intracellular recording and intracellular labeling with biocytin and other labeling materials are combined with subsequent light and electron microscopic analysis. In addition, histochemical methods, including retrograde and anterograde transport techniques, will be employed. This convergent multidisciplinary analysis will be directed to in vitro slice preparation and cultured and acutely dissociated neuron preparation obtained from rat neostriatum globus pallidus, entopeduncular nucleus, substantia nigra, and subthalamus to three sets of aims: The first set will characterize the membrane properties (including ionic conductances such as K, Na, Ca, etc.) of the neuron by the use of whole-cell (voltage) clamp technique in acutely dissociated or cultured neurons or by an intracellular current clamp recording in slice preparation. The second set will delineate the action of putative neurotransmitters or neuromodulators by monitoring changes in ionic conductances produced by the drugs or their agonists and antagonists. The transmitters to be studied are dopamine (DA), glutamate, and acetylcholine (ACh), which are the major known neurotransmitters and modulators involved in these nuclear operation. We will identify the transmitter and morphological phenotypes of the neurons under study by anatomical techniques by combined techniques of immunocytochemistry. The third set is to re-examine functional circuits involved among these nuclei (e.g., subthalamo-pallidal, striato-nigral, etc.) by trigger-averaging techniques with simultaneous recordings from the projection and its target neurons. Disequilibria of cholinergic, dopaminergic, glutaminergic, and GABAergic systems in the basal ganglia are believed involved in the pathophysiology of basal ganglia disease. The search for more specific treatments will be facilitated by a clearer understanding of the specific nature of the basal ganglia anatomy, physiology, pharmacology, and subsequent imbalance of extra-pyramidal operation.