An in vitro model of saccadic eye movement choice

项目总结/摘要 本研究计划的总体目标是了解基底神经节（BG）和上级丘的作用 (SC)在扫视眼动选择和决策中。该应用的重点是开发体外 脑切片模型，我们将扩大我们最近在体内的结果，并探讨生物物理学的电路 参与选择和决策。这项提议旨在将神经元的特性与其电路联系起来 行为，以阐明SC和BG在眼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。 在浅表SC（sSC）和中间SC中电刺激后信号传播的空间模式 SC（iSC）。这一目标将提供一个基本的评估的空间范围内和层间电路 2）评价SC活动模式中的抑制和兴奋。为此，我们将测试 存在三种特定的层间通路：从sSC延伸到 iSC，由iSC产生并延伸至sSC的抑制性通路和由sSC产生的兴奋性通路。 从iSC延伸到sSC。我们将使用电压成像结合膜片钳， 研究对sSC和iSC刺激的反应，并将这些反应分解为 谷氨酸能和GABA能突触。突触受体拮抗剂的实验将评估 在层内和层间回路中的谷氨酸能和GABA能传递; 3）确定影响 BG输出对整个SC的响应模式的影响。该目的的实验将检验以下假设： 视觉信息从sSC到iSC中运动信息的转换受到来自 黑质网状部我们将对黑质进行电刺激，以确定 黑质调节SC对sSC和iSC刺激的反应; 4）在黑质中绘制SC上的反应模式， 猴SC。我们将使用猴组织开发SC的体外制剂。实验如 将执行目标1和2。我们将测试猴子和啮齿动物的潜在回路 SC同源。由于BG及其靶结构涉及许多神经和 精神疾病状态，我们的实验结果应该导致重要的见解功能 这些电路和生物物理机制的复杂行为和认知处理， 健康和疾病。

PROJECT SUMMARY/ABSTRACT 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.