Neural circuits for adaptively biasing decision making

项目概要（摘要） 我们的长期目标是阐明大脑区域内和跨区域的系统和回路， 决策。这项建议的目的是检查神经回路的基础，如何面对 感官的不确定性，感知决策自适应地偏向于最有价值的选择，如由 最近的历史选择及其结果。我们通过关注上级丘来解决这个问题 (SC)是大脑区域网络中负责选择运动目标的关键中脑节点（即， “空间选择”），这是一种重要的决策形式，适用于电路级询问。SC整合 来自许多大脑区域的输入，具有广泛的内在回路，能够将先验与感觉整合在一起。 贝叶斯框架所要求的证据，并输出前运动定向命令到下游运动 原子核。鉴于其作为空间选择功能中心的作用，以及其已知的细胞类型和电路，SC 是理想的检查神经电路的基础，自适应决策和决策是如何影响 前科特别地，SC从中脑接收未知功能的鲁棒输入。 脚桥被盖核（PPTg），我们已经表明代表最近的空间选择， 结果。在一组行为小鼠的实验中，我们测试了SC适应性地 通过整合PPTg输入所代表的先验信息来偏置空间选择。 我们使用了一个已建立的小鼠空间选择任务的变体，其中， 在中央端口处呈现的气味混合物提示在左侧或右侧奖励端口处是否可获得奖励，并且在 其中左/右奖励比率在试验块中变化。在试验中，气味混合物只提供 弱证据奖励位置，决策可以优化偏向港口的选择 获得更大的奖励。在目标1中，我们检验了运动前SC输出偏向选择的假设。 最有价值的目标，通过记录和干扰遗传定义的前运动SC神经元的活动， 任务。在目标2中，我们测试了PPTg输入将先验的表示传输到SC的假设， 指导前运动SC神经元中适应性选择偏差。我们研究SC神经元-特别是抑制性神经元- 连合神经元很好地定位，以调解左右选择之间的竞争-代表选择 和以前试验的结果，正如我们在PPTg中所看到的。然后，我们确定是否表示 通过干扰PPTg活性和记录SC活性，SC中的先验和选择偏差依赖于PPTg输入 在任务期间。 如果成功，我们的建议的总体影响将是阐明一个关键的电路机制， 决策是由先验优化的，先验是一种关键的神经系统功能。此外，我们的建议将使未来 研究遗传定义和特定投射的神经回路如何有助于决策， 提供了对大脑基本功能和决策受损的神经系统状况的深入了解。

PROJECT SUMMARY (ABSTRACT) Our long-term goal is to elucidate the systems and circuits, within and across brain regions, responsible for decision making. The objective of this proposal is to examine the neural circuit basis for how, in the face of sensory uncertainty, perceptual decisions are adaptively biased to the most valuable option, as instructed by the recent history of choices and their outcomes. We address this question by focusing on the superior colliculus (SC), a key midbrain node in the network of brain regions responsible for selecting targets for movement (i.e., “spatial choice”), an important form of decision making amenable to circuit-level interrogation. The SC integrates input from numerous brain regions, has extensive intrinsic circuitry capable of integrating priors with sensory evidence as required by Bayesian frameworks, and outputs pre-motor orienting commands to downstream motor nuclei. Given its role as a functional hub for spatial choice, as well as its known cell types and circuitry, the SC is ideal for examining the neural circuit basis for adaptive decision making and how decisions are influenced by priors. In particular, the SC receives a robust input – of unknown function – from the mesencephalic pedunculopontine tegmental nucleus (PPTg), which we have shown represents recent spatial choices and outcomes. In a set of experiments in behaving mice, we test the overarching hypothesis that the SC adaptively biases spatial choice by integrating priors represented by PPTg input. We use a variant of an established spatial choice task for mice in which the dominant component of an odor mixture presented at a central port cues whether reward is available at the left or right reward port, and in which the left/right reward ratio changes across blocks of trials. On trials in which the odor mixture provides only weak evidence about reward location, decision making can be optimized by biasing choices towards the port yielding the larger reward. In Aim 1, we test the hypothesis that pre-motor SC output biases choice towards the most valuable target, by recording and perturbing the activity of genetically defined pre-motor SC neurons during the task. In Aim 2, we test the hypothesis that PPTg input transmits representations of priors to the SC that instruct adaptive choice bias in pre-motor SC neurons. We examine whether SC neurons – particularly inhibitory commissural neurons well positioned to mediating competition between left and right choices – represent choices and outcomes of previous trials, as we have seen in the PPTg. We then determine whether representations of priors and choice bias in the SC depend on PPTg input, by perturbing PPTg activity and recording SC activity during the task. If successful, the overall impact of our proposal will be the elucidation of a key circuit mechanism for how decisions are optimized by priors, a critical nervous system function. In addition, our proposal will enable future research into how genetically-defined and projection-specific neural circuits contribute to decision making, offering insight into basic brain function and neurological conditions in which decision making is impaired.