An in vitro model of saccadic eye movement choice

 描述(由申请人提供)最近在理解大脑皮层微循环方面取得了长足的进步。转基因和光遗传学的引入，以及膜片钳技术的进步，对快速发现起到了重要作用。例如，我们现在知道大脑皮层中至少有三种类型的抑制性中间神经元：那些表达钙结合蛋白(PV)的神经元，以及那些使用多肽神经调节剂血管活性肠肽(VIP)或生长抑素(SOM)的神经元。对这些神经元进行独特的标记表明，这些抑制性中间神经元存在于大脑皮层的大部分区域。它们具有不同的形态，终止于输出神经元的不同部分，具有不同的突触强度，在信息处理中扮演不同的角色。在这一应用中，我们建议利用转基因和光遗传学的最新进展来揭示上丘内抑制微电路的结构和功能，以及外部输入在调制这些电路中所起的作用。我们有三个目标。首先，确定丘脑微路视感层局部小白蛋白(PV)表达神经元的生理和靶点。这些实验将验证这样一种假设，即PV神经元对感觉神经元提供了主要的抑制来源，从而产生了丘脑-枕叶-皮质通路和下行的椎板内通路到运动层。第二，确定外源性GABA能从黑质网状部传入运动层丘脑微回路的生理和靶点。这些 实验将检验来自黑质的外部抑制是主要来源的假设。 对上丘微回路中运动输出神经元的抑制。第三，确定 丘脑微电路的PV和黑质GABA能输入的功能。我们将检验这一假设，即来自PV神经元的抑制和来自黑质的抑制在决定感觉神经元和运动神经元的丘神经元的反应增益中发挥不同的作用。由于PV神经元与神经精神疾病的过程有关，我们的实验结果应该会阐明这些神经元如何促进更高的精神功能。

 DESCRIPTION (provided by applicant) 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.