An in vitro model of saccadic eye movement choice

眼跳眼动选择的体外模型

• 批准号: 8538980
• 负责人: Michele A Basso
• 金额: $ 34.47万
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8538980
• 关键词: Accounting; Area; Attention Deficit Disorder; Basal Ganglia; Basal Ganglia Diseases; Behavior; Behavioral; Biophysics; Brain; Cells; Choice Behavior; Cognitive; Complex; Decision Making; Diagnostic; Disease; Electric Stimulation; Eye; Eye Movements; Fiber; Fluorescent Dyes; Generations; Gilles de la Tourette syndrome; Glutamates; Goals; Health; Image; In Vitro; Individual; Lateral; Lead; Ligands; Link; Maps; Measures; Mediating; Membrane; Mental Processes; Mental disorders; Methods; Midbrain structure; Modeling; Monkeys; Morphology; Motor; Neurons; Obsessive-Compulsive Disorder; Output; Parietal; Pathway interactions; Pattern; Perception; Physiology; Play; Population; Preparation; Primates; Process; Property; Psyche structure; Research; Rodent; Role; Saccades; Schizophrenia; Signal Transduction; Slice; Structure; Substantia nigra structure; Synapses; Synaptic Receptors; Testing; Thinking; Tissues; Translations; Visual; Wisconsin; Work; base; brain tissue; cognitive neuroscience; frontal eye fields; in vitro Model; in vivo; insight; lateral intraparietal area; nervous system disorder; neural circuit; neurobiotin; patch clamp; public health relevance; research study; response; superior colliculus Corpora quadrigemina; transmission process; visual information; voltage

DESCRIPTION (provided by applicant): The overall goal of this research plan is to understand the role of the basal ganglia (BG) and superior colliculus (SC) in saccadic eye movement choice and decision-making. This application focuses on developing an in vitro brain slice model with which we will extend our recent in vivo results and investigate the biophysics of a circuit involved in choice and decision-making. This proposal aims to link the properties of neurons and their circuits to behavior in order to elucidate the role of the SC and the BG in eye-movement related cognitive processes. We have four specific aims; 1) Map response patterns across the SC. Voltage imaging will be used to map the spatial patterns of signal spread following electrical stimulation in the superficial SC (sSC) and intermediate SC (iSC). This aim will provide a basic assessment of the spatial extent of both intra- and inter-laminar circuitry within the SC; 2) Evaluate inhibition and excitation in SC activity patterns. In this aim we will test for the existence of three specific interlaminar pathways: an excitatory pathway arising from the sSC extending to the iSC, an inhibitory pathway arising from the iSC and extending into the sSC and an excitatory pathway arising from the iSC and extending into the sSC. We will use voltage imaging in conjunction with patch clamping to study responses to sSC and iSC stimulation, and resolve these responses into contributions mediated by glutamatergic and GABAergic synapses. Experiments with synaptic receptor antagonists will assess the role of glutamatergic and GABAergic transmission in both intra- and interlaminar circuits; 3) Determine the influence of BG output on the response pattern across the SC. The experiments of this aim will test the hypothesis that translation of visual information from sSC into motor information in iSC is modulated by inhibition from the substantia nigra pars reticulata of the BG. We will apply electrical stimulation in the nigra to determine how the nigra modulates SC responses to sSC and iSC stimulation; 4) Map response patterns across the SC in monkey SC. We will develop an in vitro preparation of the SC using monkey tissue. Experiments as outlined in aims 1 and 2 will be performed. We will test the hypothesis that the underlying circuits in monkey and rodent SC are homologous. Because the BG and its target structures are implicated in many neurological and psychiatric disease states, the results of our experiments should lead to important insights into the functioning of these circuits and the biophysical mechanisms underlying complex behavioral and cognitive processing in both health and disease.

描述（由申请人提供）：本研究计划的总体目标是了解基底神经节（BG）和上丘（SC）在眼跳选择和决策中的作用。该应用程序的重点是开发体外脑切片模型，我们将利用该模型扩展我们最近的体内结果并研究涉及选择和决策的回路的生物物理学。该提案旨在将神经元及其回路的特性与行为联系起来，以阐明 SC 和 BG 在与眼球运动相关的认知过程中的作用。我们有四个具体目标； 1) 绘制整个 SC 的响应模式。电压成像将用于绘制浅表 SC (sSC) 和中间 SC (iSC) 电刺激后信号传播的空间模式。这一目标将对 SC 内层内和层间电路的空间范围进行基本评估； 2) 评估 SC 活动模式的抑制和兴奋。为此，我们将测试三种特定层间通路的存在：从 sSC 产生并延伸到 iSC 的兴奋性通路、从 iSC 产生并延伸到 sSC 的抑制性通路以及从 iSC 产生并延伸到 sSC 的兴奋性通路。我们将使用电压成像与膜片钳结合来研究对 sSC 和 iSC 刺激的反应，并将这些反应解析为由谷氨酸能和 GABA 能突触介导的贡献。突触受体拮抗剂的实验将评估谷氨酸能和 GABA 能传递在层内和层间回路中的作用； 3) 确定 BG 输出对整个 SC 响应模式的影响。该目的的实验将检验以下假设：从 sSC 的视觉信息到 iSC 中的运动信息的翻译是通过 BG 黑质网状部的抑制来调节的。我们将在黑质中施加电刺激，以确定黑质如何调节 SC 对 sSC 和 iSC 刺激的反应； 4) 绘制猴子 SC 中整个 SC 的反应模式。我们将使用猴组织开发 SC 的体外制剂。将进行目标 1 和 2 中概述的实验。我们将检验猴子和啮齿动物 SC 的基础电路是同源的假设。由于 BG 及其目标结构与许多神经和精神疾病状态有关，因此我们的实验结果应该有助于深入了解这些回路的功能以及健康和疾病中复杂行为和认知处理背后的生物物理机制。