An in vitro model of saccadic eye movement choice

眼跳眼动选择的体外模型

• 批准号: 9198228
• 负责人: Michele A Basso
• 金额: $ 46.24万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9198228
• 关键词: Afferent Neurons; Anatomy; Area; Attention Deficit Disorder; Award; Behavior; Binding Proteins; Brain; Brain Stem; Cells; Cerebral cortex; Cerebrum; Characteristics; Choice Behavior; Cues; Decision Making; Diagnostic; Disease; Electrophysiology (science); Elements; Eye Movements; Gilles de la Tourette syndrome; Image; In Vitro; Interneurons; Knock-in Mouse; Label; Laboratories; Lead; Maps; Measures; Mental disorders; Midbrain structure; Monkeys; Morphology; Motor; Motor Neurons; Motor output; Mus; Neuromodulator; Neurons; Obsessive-Compulsive Disorder; Output; Parvalbumins; Patch-Clamp Techniques; Pathway interactions; Peptides; Physiological; Physiology; Play; Process; Property; Pulvinar structure; Research; Rhodopsin; Role; Saccades; Schizophrenia; Sensory; Series; Short Interspersed Nucleotide Elements; Signal Transduction; Slice; Somatostatin; Source; Staining method; Stains; Structure; Study models; Substantia nigra structure; Synapses; Techniques; Testing; Transgenic Mice; Transgenic Organisms; Vasoactive Intestinal Peptide; Visual; Whole-Cell Recordings; Work; cell type; experimental study; frontal eye fields; gamma-Aminobutyric Acid; gaze; genetic manipulation; immunocytochemistry; in vitro Model; in vivo; information processing; insight; lateral intraparietal area; mental function; mouse model; nervous system disorder; neuropsychiatric disorder; optogenetics; public health relevance; response; superior colliculus Corpora quadrigemina; visual process

 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.

 最近在理解大脑皮层微电路方面已经取得了很大的进展。转基因和光遗传学的引入以及膜片钳技术的进步，有助于快速发现。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：表达Ca++结合蛋白小清蛋白（PV）的抑制性中间神经元，以及使用肽神经调节剂血管活性肠肽（VIP）或生长抑素（SOM）的抑制性中间神经元。唯一标记这些神经元揭示了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位，具有不同的突触强度，并且它们在信息处理中发挥不同的作用。在这个应用中，我们建议利用转基因和光遗传学的最新进展，揭示抑制性微电路的结构和功能的上级丘和外部输入的作用，在调制这些电路。我们有三个目标。首先，确定生理学和局部小白蛋白（PV）表达神经元在视觉感觉层的丘微回路的目标。这些实验将检验PV神经元提供对感觉神经元抑制的主要来源的假设，所述感觉神经元引起丘-枕-皮质通路和下行的板内通路至运动层。第二，确定从黑质网状部（黑质）到运动层丘微回路的外源性GABA能输入的生理学和靶点。这些 实验将检验来自黑质的外部抑制是主要来源的假设 抑制上级丘微回路中的运动输出神经元。第三，确定 PV和黑质GABA能输入到丘微电路的功能。我们将测试的假设，从PV神经元的抑制和黑质的抑制在确定感觉和运动神经元的丘神经元的反应增益发挥不同的作用。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澄清这些神经元如何有助于更高的精神功能。