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

描述（由申请人提供）：给定相同的感官信息，我们在不同的情况下会产生不同的反应，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。本研究的主要目的是阐明门控计算和柔性感觉-运动映射在决策中的计算原理和电路基础。我认为门控是通过四种互补机制来完成的：(a)输入门控由GABAergic神经元的一个子类来调节树突抑制，(b)离散阶段处理的“通路特异性兴奋-抑制平衡”，(c)网络选择规则表示的自上而下信号传导，(d)自动反应的抑制控制的“STOP”过程。我将在基于生物学的电路模型中严格研究这些机制，与正在进行猴子执行灵活的视觉运动任务的单神经元生理实验的实验学家合作。在控制动作的范式任务中，对感觉目标的适当反应是根据任务情境将目光移向它（前扫视）或移离它（反扫视）。在“有色目标”任务中，必须在受试者知道何时以及如何使用该决定来指导行动选择之前，对模糊刺激或基于感官线索的概率推断做出感知决定。我们的模型将通过定量再现单个神经元的活动数据和行为表现来进行测试，并揭示潜在的回路机制，这些机制将在新的实验中进行测试。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”的想法。目标二是

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.