Leveraging multisensory decisions to understand brain wide decision circuits

利用多感官决策来理解大脑范围的决策回路

基本信息

批准号：
9913536
负责人：
ANNE KATHRYN CHURCHLAND
金额：
$ 15.51万
依托单位：
COLD SPRING HARBOR LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9913536
关键词：
Address Animals Area Auditory Behavior Behavioral Brain Clinical Cognition Disorders Common Core Data Decision Making Discrimination Disease Event Fluorescence Foundations Goals Heterogeneity Human Image Individual Knowledge Lead Left Light Link Maintenance Mammals Measurement Measures Mediating Methods Modality Modeling Motor Cortex Motor output Mus Neurons Optical Methods Outcome Parietal Lobe Parkinson Disease Population Population Heterogeneity Property Rattus Research Rodent Role Schizophrenia Sensory Signal Transduction Source Stimulus Structure Testing Time Training Transgenic Mice Visual Work auditory stimulus autism spectrum disorder base calcium indicator cell type control trial excitatory neuron experimental study inhibitory neuron multisensory neuromechanism novel therapeutic intervention optogenetics programs relating to nervous system response two photon microscopy two-photon visual stimulus

项目摘要

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.

拟议研究的目标是揭示大脑范围的电路和局部计算让动物能够结合多种不同的信息源来指导具体来说，这些实验将研究哺乳动物如何整合。随着时间的推移和跨感觉模式的感觉信号。除了特定感觉回路之外，听觉和视觉决策还依赖于共同的核心决策用于决策相关计算的电路，例如证据积累和行动选择。在这些结构中，兴奋性和抑制性神经元之间有针对性的连接支持持续的活动和动作选择的竞争所提出的测试方法。该假设是为了测量和操纵经过训练的小鼠的神经活动，以产生知觉关于听觉和视觉刺激的决策的核心是三种方法。该提案评估了这一假设并提供了决策电路的新观点。首先，听觉和视觉决策激活重叠或很大程度上分离的程度神经结构将基于皮质范围活动的广域成像进行评估将在表达钙的转基因小鼠中测量整个皮质的活动。我们将使用的皮质兴奋性神经元的指标。这种方法将给定大脑结构中的活动与决策计算联系起来。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学抑制将用于评估它们的因果关系基于模型的抑制和控制行为比较。试验将评估中断对决策相关计算（例如事件）的影响歧视、证据积累和行动规划。最后，将调查被确定为特定决策计算的因果区域更深入地了解这些计算是如何由单个神经元实现的 2-。光子显微镜将用于对单个神经元群体进行成像。受试者将是转基因小鼠，其中抑制性神经元发出红色荧光，即与用作神经活动估计的绿色荧光无关。单独的信号使得能够区分兴奋性神经元和抑制性神经元并评估它们在决策中各自的作用将用于评估单次试验分类器。兴奋性和抑制性群体预测动物选择结果的能力。实验将用于区分候选决策模型。