Leveraging multisensory decisions to understand brain wide decision circuits

这项拟议的研究的目标是揭示大脑的广泛回路和局部计算 它们一起允许动物结合多种不同的信息来源来指导 决策。具体地说，这些实验将研究哺乳动物是如何整合 随着时间的推移和跨感觉模式的感觉信号。主要的假设是，在 除了特定于感觉的回路外，听觉和视觉判断还依赖于共同的核心判断 用于决策相关计算的电路，如证据积累和行动选择。 在这些结构中，兴奋性神经元和抑制性神经元之间的定向连接 支持持续的活动和竞争的行动选择。建议的测试方法 这一假设是为了测量和操纵经过训练的小鼠的神经活动，使其具有知觉 关于听觉和视觉刺激的决定。三种方法结合在一起，构成了 评估这一假说并提供决策回路的新视角的提议。 首先，听觉和视觉判断激活重叠或主要分离的程度 神经结构将基于大脑皮质活动的大范围成像进行评估 决策。将在表达钙的转基因小鼠中测量整个皮质的活动。 皮质兴奋性神经元中的指示物。我们将使用的分类器和决策模型 将给定大脑结构中的活动与决策计算联系起来。这一方法将 发现在听觉、视觉或多感官决策过程中活跃的候选区域。 接下来，这些候选区域的光遗传抑制将被用来评估它们的原因 在决策中的作用。基于模型的抑制和控制行为比较研究 试验将评估中断对与决策相关的计算的影响，如事件 歧视、证据积累和行动计划。 最后，将调查被确定为特定决策计算的因果关系的区域 更近距离地了解这些计算是如何由单个神经元实现的。2- 光子显微镜将被用于对单个神经元的群体进行成像。实验性的 受试者将是转基因小鼠，在转基因小鼠中，抑制神经元发出红色荧光，这是 与绿色荧光无关，绿色荧光被用来估计神经活动。这两个 分离的信号可以区分兴奋性神经元和抑制性神经元，并评估 他们在决策中的各自角色。将使用单次试验分类器来评估 兴奋性和抑制性种群预测动物选择的能力。这样做的结果是 实验将用于区分决策的候选模型。

The goal!of the proposed research is to uncover the brain wide circuits and local computations that together allow animals to combine multiple, diverse sources of information to guide decision-making. Specifically, these experiments will investigate how mammals integrate sensory signals over time and across sensory modalities. The main hypothesis is that in addition to sense-specific circuits, auditory and visual decisions rely on common, core decision circuits for decision-related computations, such as evidence accumulation and action selection. Within these structures, targeted connectivity between excitatory and inhibitory neurons supports persistent activity and competition for action selection. The proposed method to test this hypothesis is to measure and manipulate neural activity in mice trained to make perceptual decisions about auditory and visual stimuli. Three approaches, taken together, form the core of the proposal to evaluate this hypothesis and provide a new view of decision-making circuits. First, the degree to which auditory and visual decisions activate overlapping or largely separate neural structures will be evaluated based on wide field imaging of cortex-wide activity during decision-making. Cortex-wide activity will be measured in transgenic mice that express calcium indicators in cortical excitatory neurons. Classifiers and decision-making models we will used to link activity in a given brain structure to decision-making computations. This approach will uncover candidate areas that are active during auditory, visual or multisensory decisions. Next, optogenetic suppression of these candidate areas will be used to evaluate their causal role in decision-making. A model-based comparison of behavior on suppression and control trials will evaluate the effects of disruption on decision-related computations such as event discrimination, evidence accumulation, and action planning. Finally, areas that are identified as causal for specific decision computations will be investigated more closely to understand how these computations are implemented by single neurons. 2- photon microscopy will be used to image populations of single neurons. The experimental subjects will be transgenic mice in which inhibitory neurons emit red fluorescent light that is independent of the green fluorescence that is used as an estimate of neural activity. These two separate signals make it possible to distinguish excitatory from inhibitory neurons and evaluate their respective roles in decision-making. Single-trial classifiers will be used to evaluate the ability of excitatory and inhibitory populations to predict the animal’s choice. The outcome of this experiment will be used to distinguish candidate models of decision-making.