Gated sensori-motor mapping and cortical circuit reconfiguration in flexible deci

描述（由申请人提供）：给定相同的感觉信息，我们在不同的情况下产生不同的反应，这取决于我们的目标，任务规则等。这种灵活性是认知的标志，涉及大脑回路中信息流的门控路由，其潜在机制在很大程度上仍然是神秘的。该研究的总体目标是阐明门控计算和灵活的感觉-运动映射在决策中的计算原理和电路基础。我认为门控是由四种互补机制完成的：（a）GABA能神经元的一个亚类对输入门控的可调树突抑制，（B）离散阶段加工的“通路特异性兴奋-抑制平衡”，（c）网络选择的规则表征的自上而下的信号传递，（d）自动反应抑制控制的“STOP”过程。我将严格调查这些机制在生物学为基础的电路模型，与实验学家谁正在进行单神经元生理实验中，猴子执行灵活的视觉运动任务的合作。在控制动作的范例任务中，对感觉目标的适当反应是根据任务上下文将目光移向它（亲扫视）或远离它（反扫视）。在“有色目标”任务中，必须对模糊的刺激或基于感官线索的概率推理做出感知决定，然后受试者才知道何时以及如何使用该决定来指导动作选择。我们的模型将通过定量再现单神经元活动数据以及行为表现来进行测试，并揭示在新实验中可测试的潜在电路机制。在目标1中，我将研究门控的电路机制，包括输入特异性树突抑制和“通路特异性兴奋-抑制平衡”的概念。目标2将是 致力于基于规则的动作选择，通过开发一个详细的电路模型的亲/反眼跳任务。在目标3中，我将研究感知决策和动作选择在时间上分离时的门控神经动力学。我们将为随机点运动方向辨别任务和天气预测任务的版本构建尖峰网络模型。亲/反扫视和彩色目标视觉运动任务都依赖于从感觉决策电路到动作选择电路的信息的灵活路由，这赋予了该应用程序很强的凝聚力。这项研究计划将深入了解具有混合选择性的神经元的复杂动力学，这些选择性是灵活行为中自适应编码的基础。

DESCRIPTION (provided by applicant): Given the same sensory information, we generate different responses in different situations, depending on our goal, task rule, etc. This flexibilit is a hallmark of cognition and involves gated routing of information flow in the brain circuitry, the underlying mechanism remains largely mysterious. The overarching objective of the proposed research is to elucidate computational principles and circuit basis of gated computation and flexible sensori-motor mapping in decision-making. I propose that gating is accomplished by four complementary mechanisms: (a) tunable dendritic inhibition by a subclass of GABAergic neurons for input gating, (b) "pathway-specific excitation-inhibition balance" for processing in discrete stages, (c) top-down signaling from rule representation for network selection, (d) a "STOP" process for inhibitory control of automatic response. I will rigorously investigate these mechanisms in biologically based circuit models, in collaboration with experimentalists who are carrying out single-neuron physiological experiments in which monkeys perform flexible visuo-motor tasks. In a paradigmatic task of controlled action, the appropriate response to a sensory target is to either shift the gaze toward it (pro-saccade) or away from it (anti-saccade) depending on task context. In "colored-target" tasks, a perceptual decision about an ambiguous stimulus or a probabilistic inference based on sensory cues must be made, before the subject knows when and how the decision will be used to guide action selection. Our model will be tested by quantitatively reproducing single-neuron activity data as well as behavioral performance, and uncovering the underlying circuit mechanisms that will be testable in new experiments. In Aim 1, I will examine circuit mechanisms for gating, including input-specific dendritic inhibition and the idea of "pathway-specific excitation-inhibition balance. Aim 2 will be devoted to rule-based action selection, by developing a detailed circuit model of the pro-/anti-saccade task. In Aim 3, I will examine gated neural dynamics when perceptual decision and action selection are temporally separated. We will build spiking network models for versions of the random dot motion direction discrimination task and weather prediction task. The pro-/anti-saccade and colored-target visuo-motor tasks all depend on flexible routing of information from a sensory decision circuit to an action selection circuit, which confers a strong cohesiveness to this application. This research program will shed insights into complex dynamics of neurons endowed with mixed selectivity that underlie adaptive coding in flexible behavior.