Cortical control of striatal cell activity

描述(由申请人提供) 精神分裂症、帕金森氏病、多发性抽动症、强迫症和毒瘾只是与脑多巴胺系统功能障碍和纹状体皮质输入异常处理有关的部分临床症状。在纹状体神经元对皮质输入的精细结构做出反应的强健的膜电位去极化(Up状态)是由皮质本身调用的突触驱动事件，可能由多巴胺调节的膜电流形成。纹状体表现为“行为选择”网络的建议，提高了人们对了解纹状体中如何表现出皮质活动的动态模式，以及这种表现如何被多巴胺神经传递的变化所改变的兴趣。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UP状态的时间动力学的一些方面。在这个方案中，我们计划通过记录麻醉大鼠多个皮质部位的场电位和多单位活动以及纹状体神经元的膜电位，来分析纹状体神经元上皮层活动的空间变化。我们的主要目标是了解纹状体神经元的膜电位(作为突触输入的指标)和放电模式(作为神经元输出的指标)如何反映皮质活动的空间分布和动态变化模式。此外，我们还将研究皮层活动对缺乏功能性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布宜诺斯艾利斯大学医学院与M.Gustavo Murer合作进行，作为NIH#R01MH060131号赠款的延伸。

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.