An in vitro model of saccadic eye movement choice

项目摘要 最近在理解大脑皮层微电路方面取得了很大进展。引入 转基因和光遗传学以及膜片钳技术的进步，已经在 快速发现。例如，我们现在知道，至少有三种类型的抑制性中间神经元， 大脑皮层：表达Ca++结合蛋白小清蛋白（PV）的大脑皮层，以及使用 肽神经调节剂血管活性肠肽（VIP）或生长抑素（SOM）。独特地标记这些 神经元的研究表明，这些抑制性中间神经元存在于大脑皮层的大部分区域。他们有不同 形态，终止于输出神经元的不同部分，具有不同的突触强度， 信息处理中的不同角色。在本申请中，我们建议利用最近的进展， 转基因和光遗传学，以揭示结构和功能的抑制性微电路内的上级 以及外部输入在调节这些回路中的作用。我们有三个目标。一是确定 在视感觉层的局部小白蛋白（PV）表达神经元的生理和目标， 丘状微电路这些实验将检验PV神经元提供主要来源的假设 抑制引起丘-枕-皮层通路和下行神经元的感觉神经元， 到运动层的板内通路。第二，确定外源性GABA能的生理学和靶点， 从黑质网状部（黑质）到运动层丘微回路的输入。这些 实验将检验来自黑质的外部抑制是抑制的主要来源这一假设 对上级丘微回路中运动输出神经元的影响。第三，确定PV的功能， 黑质GABA能输入到丘微电路。我们将检验PV神经元的抑制 黑质的抑制在决定感觉神经元的反应增益中起着不同的作用 和运动神经元。由于PV神经元与神经精神疾病过程有关， 我们的实验结果应该可以阐明这些神经元是如何对高级心理功能做出贡献的。

PROJECT SUMMARY Great strides have been made recently in understanding cerebral cortical microcircuits. The introduction of transgenics and optogenetics together with advances in patch clamp techniques, have been instrumental in the rapid rate of discovery. For example, we now know there are at least three types of inhibitory interneurons in the cerebral cortex: those that express the Ca++ binding protein parvalbumin (PV), and those that use either the peptide neuromodulator vasoactive intestinal peptide (VIP) or somatostatin (SOM). Uniquely labeling these neurons reveals that these inhibitory interneurons exist in most areas of cerebral cortex. They have different morphologies, terminate on different parts of output neurons, have differing synaptic strengths and they play different roles in information processing. In this application, we propose to capitalize on the recent advances in transgenics and optogenetics to reveal the structure and function of inhibitory microcircuits within the superior colliculus and the role external inputs play in modulating these circuits. We have three aims. First, determine the physiology and targets of the local parvalbumin (PV) expressing neurons in the visuosensory layer of the collicular microcircuit. These experiments will test the hypothesis that PV neurons provide the dominant source of inhibition on sensory neurons that give rise to the colliculo-pulvinar-cortical pathway and to the descending intralaminar pathway to the motor layer. Second, determine the physiology and targets of extrinsic GABAergic inputs from the substantia nigra pars reticulata (nigra) to the motor layer collicular microcircuit. These experiments will test the hypothesis that external inhibition from the nigra is the dominant source of inhibition on motor output neurons in the superior colliculus microcircuit. Third, determine the function of the PV and nigral GABAergic inputs to collicular microcircuits. We will test the hypothesis that inhibition from PV neurons and inhibition from the nigra play different roles in determining response gain of collicular neurons in sensory and motor neurons. Because PV neurons have been implicated in neuropsychiatric disease processes the results of our experiments should clarify how these neurons contribute to higher mental function.