An in vitro model of saccadic eye movement choice

眼跳眼动选择的体外模型

• 批准号: 7988016
• 负责人: Michele A Basso
• 金额: $ 34.55万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7988016
• 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; Neurologic; 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; 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. PUBLIC HEALTH RELEVANCE: A sine qua non of higher mental function is our ability to make decisions. Extreme fluctuations in choice behavior may underlie certain neurological and psychiatric diseases such as schizophrenia, attention deficit disorder, Tourette Syndrome and obsessive compulsive disorder. Eye movement abnormalities are also associated with these cortico-basal ganglia diseases. Therefore, a deeper understanding of the basal ganglia - superior colliculus pathway and circuitry and ultimately their role in higher mental function, may lead to better diagnostics, better ways to assess therapies and should provide important insights into the mechanisms of symptomology in these disease states.

描述（由申请人提供）：该研究计划的总体目标是了解基底神经节（BG）和上丘的角色（SC）在Saccadic眼动运动的选择和决策中的作用。该应用的重点是开发一个体外脑切片模型，我们将扩展我们最近的体内结果，并研究参与选择和决策的电路的生物物理学。该建议旨在将神经元及其电路的特性与行为联系起来，以阐明SC和BG在与眼动相关的认知过程中的作用。我们有四个具体的目标； 1）跨SC的映射响应模式。电压成像将用于绘制浅表SC（SSC）和中间SC（ISC）电刺激后信号扩散的空间模式。该目标将对SC内层间和层间电路的空间范围提供基本评估； 2）评估SC活性模式中的抑制和激发。在此目标中，我们将测试存在三种特定的层间途径：由SSC延伸到ISC产生的兴奋性途径，这是由ISC引起的抑制途径，并延伸到SSC，并延伸到SSC，并引起了ISC引起的兴奋性途径并延伸到ISC中。 SSC。我们将使用电压成像与斑块夹紧来研究对SSC和ISC刺激的反应，并将这些响应解决为谷氨酸能和GABAergic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能传播在内部和层间电路中的作用； 3）确定BG输出对SC跨SC的响应模式的影响。该目标的实验将检验以下假设：将视觉信息从SSC转化为ISC中的运动信息是通过BG的底层网状网状抑制调节的。我们将在NIGRA中应用电刺激，以确定NIGRA如何调节SC对SSC和ISC刺激的反应； 4）Monkey SC中SC的地图响应模式。我们将使用猴子组织在体外制备SC。将进行AIMS 1和2中概述的实验。我们将检验以下假设：猴子和啮齿动物SC中的基础电路是同源的。由于BG及其目标结构与许多神经系统和精神疾病状态有关，因此我们实验的结果应导致对这些电路功能以及健康和疾病中复杂行为和认知处理的生物物理机制的重要见解。 公共卫生相关性：我们做出决策的能力是我们的精神功能较高的正弦。选择行为的极端波动可能是某些神经系统和精神疾病的基础，例如精神分裂症，注意力缺陷障碍，图雷特综合症和强迫症。眼睛运动异常也与这些皮质 - 基质神经节疾病有关。因此，对基底神经节的更深入了解 - 上丘陵途径和电路，最终在更高的心理功能中的作用，可能会导致更好的诊断，更好地评估疗法的方法，并应提供对这些疾病状态症状机制的重要见解。