INTERNEURONAL MICROCIRCUITRY OF THE RAT NEOSTRIATUM

描述(摘自申请者的摘要)：基底节为 关键参与运动行为和感觉运动的组织 整合。人类这一系统的故障导致了 神经精神障碍的病理生理学，如精神分裂症和 强迫症，以及神经疾病，如 亨廷顿和帕金森氏症。了解信息 在此系统内以机械术语进行处理需要 对关节的生理特性和解剖结构的了解 它的组成原子核的微电路。最大的新纹状体 基底节核团在控制脑电活动中起中心作用。 基底节的功能，因此，对 这个核团的内在运作对于理解 基底节的信息处理。最近，它一直在 越来越多的人认识到，从数量上讲， 新纹状体的GABA能中间神经元可能在 主细胞群体活动的组织。然而， 直到最近引入了视觉引导全细胞记录这些 无法接触到神经元进行生理学研究。在 建议的研究，这项强大的技术将与 细胞内染色及光镜和电子显微镜分析 分析这些中间神经元在控制神经元活动中的作用 它们的主要突触后目标是中等刺神经元。同时进行 配对的录音将从中间神经元和中等刺细胞中获得 这些神经元将被染色，以进行进一步的解剖学研究。这个 将讨论以下具体问题。首先，什么是本质 两种主要类型的抑制性神经元之间的突触相互作用 中间神经元和中等棘神经元？第二，什么是生理上的 以及中棘抑制性输入的解剖学特化 来自不同类型中间神经元的神经元？第三，是什么模式？ 中间神经元和中棘神经元群体之间的连通性 (即收敛和发散)？最后，什么是生理上的 中间神经元之间的电耦合特性，一个潜在的 影响这些细胞群体活动的重要机制，如 那么，中等刺状神经元呢？这些数据将有助于理解 这些中间神经元对大脑中脑活动组织的贡献 新纹状体。

DESCRIPTION (Adapted from applicant's abstract): The basal ganglia are critically involved in the organization of motor behavior and sensorimotor integration. Malfunctions of this system in humans contribute to the pathophysiology of neuropsychiatric disorders such as schizophrenia and obsessive compulsive disorder, as well as to neurological diseases such as Huntington's and Parkinson's disease. Understanding the information processing within this system in mechanistic terms requires the understanding of the physiological properties and anatomical organization of the microcircuitry of its constituent nuclei. The neostriatum, the largest nucleus of the basal ganglia has a central role in controlling the functioning of the basal ganglia and therefore, an understanding of the intrinsic operations of this nucleus is critical to understanding information processing in the basal ganglia. Recently, it has been increasingly recognized that the quantitatively minor population of GABAergic interneurons of the neostriatum may play a critical role in the organization of the population activity of the principal cells. However, until the recent introduction of visually guided whole cell recording these neurons were not accessible for physiological investigation. In the proposed study, this powerful technology will be used in combination with intracellular staining and light and electron microscopic analysis to analyze the role of these interneurons in the control of the activity of their principal postsynaptic targets, the medium spiny neuron. Simultaneous paired recordings will be obtained from interneurons and medium spiny cells and the neurons will be stained for further anatomical investigation. The following specific questions will be addressed. First, what is the nature of the synaptic interaction between the two major types of inhibitory inteneurons and the medium spiny neuron? Second, what are the physiological and anatomical specializations of the inhibitory inputs to the medium spiny neuron from different types of interneurons? Third, what is the pattern of connectivity among the populations of interneurons and medium spiny neurons (i.e. convergence and divergence)? Finally, what are the physiological properties of electrical coupling between interneurons, a potentially significant mechanism affecting the population activity of these cells, as well as, the medium spiny neurons? This data will help in understanding the contribution of these interneurons to the organization of activity in the neostriatum.