Cortical control of striatal cell activity

描述（由申请人提供） 精神分裂症、帕金森病、图雷特综合征、强迫症和药物成瘾只是与脑多巴胺系统功能障碍和纹状体中皮质输入处理异常有关的一些相关临床病症。纹状体神经元对皮层输入的精细结构产生反应的强大的膜电位去极化（“上升状态”）是由皮层本身引起的突触驱动事件，并且可能由多巴胺调节的膜电流形成。纹状体作为一个“动作选择”网络的建议，引起了人们对理解皮质活动的动态模式如何在纹状体中表现以及这种表现如何通过多巴胺神经传递的变化进行修改的兴趣。通过同时记录皮层神经元的群体活动和纹状体神经元的膜电位，我们最近澄清了一些方面的时间动态的状态。在这个建议中，我们计划分析的代表性的空间变化的皮层活动纹状体神经元记录场电位和多单位活动从多个皮层网站连同膜电位的纹状体神经元在麻醉大鼠。我们的主要目标是了解空间分布和动态变化的模式的皮层活动是如何反映在膜电位（作为突触输入的指数）和放电模式（作为神经元输出的指数）的纹状体神经元。此外，我们将研究皮质活动对缺乏功能性D1或D2多巴胺受体的转基因小鼠纹状体神经元的影响。这项研究将主要在阿根廷的布宜诺斯艾利斯大学医学院进行，与M。Gustavo Murer，作为NIH资助# R01MH060131的扩展。

DESCRIPTION (provided by applicant) Schizophrenia, Parkinson's disease, Tourette's syndrome, obsessive-compulsive disorder and drug addiction, are only some of the relevant clinical conditions that have been related to dysfunction of brain dopamine systems and abnormal processing of cortical input in the striatum. The robust membrane potential depolarizations ("up states") during which striatal neurons become responsive to the fine structure of cortical input, are synaptically-driven events invoked by the cortex itself and probably shaped by dopamine-regulated membrane currents. The suggestion that the striatum behaves as an "action selection" network, raised interest in understanding how dynamic patterns of cortical activity are represented in the striatum and how this representation is modified by changes in dopamine neurotransmission. By simultaneously recording the population activity of cortical neurons and the membrane potential of striatal neurons, we have recently clarified some aspects of the temporal dynamics of up states. In this proposal, we plan to analyze the representation of spatial variations of cortical activity on striatal neurons by recording field potentials and multiunit activity from multiple cortical sites together with the membrane potential of striatal neurons in anesthetized rats. Our main goal is to understand how spatially-distributed and dynamically-changing patterns of cortical activity are reflected in the membrane potential (as an index of synaptic input) and firing pattern (as an index of neuronal output) of striatal neurons. Furthermore, we will investigate the impact of cortical activity on striatal neurons in genetically-modified mice lacking functional D1 or D2 dopamine receptors. This research will be done primarily in Argentina, at the Buenos Aires University School of Medicine, in collaboration with M. Gustavo Murer, as an extension of NIH grant # R01MH060131.