Leveraging multisensory decisions to understand brain wide decision circuits
Leveraging multisensory decisions to understand brain wide decision circuits
批准号:
9913536
负责人:
ANNE KATHRYN CHURCHLAND
金额:
$15.51万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-03-01 至 2020-08-31
关键词:
AddressAnimalsAreaAuditoryBehaviorBehavioralBrainClinicalCognition DisordersCommon CoreDataDecision MakingDiscriminationDiseaseEventFluorescenceFoundationsGoalsHeterogeneityHumanImageIndividualKnowledgeLeadLeftLightLinkMaintenanceMammalsMeasurementMeasuresMediatingMethodsModalityModelingMotor CortexMotor outputMusNeuronsOptical MethodsOutcomeParietal LobeParkinson DiseasePopulationPopulation HeterogeneityPropertyRattusResearchRodentRoleSchizophreniaSensorySignal TransductionSourceStimulusStructureTestingTimeTrainingTransgenic MiceVisualWorkauditory stimulusautism spectrum disorderbasecalcium indicatorcell typecontrol trialexcitatory neuronexperimental studyinhibitory neuronmultisensoryneuromechanismnovel therapeutic interventionoptogeneticsprogramsrelating to nervous systemresponsetwo photon microscopytwo-photonvisual stimulus
中文摘要
进球了!这项研究的目的是揭示大脑的广泛回路和局部计算,
使动物能够联合收割机结合多种多样的信息来源,
决策的具体来说,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态的感觉信号。主要假设是,
除了感觉特定的电路,听觉和视觉决策依赖于共同的核心决策,
用于决策相关计算的电路,例如证据积累和动作选择。
在这些结构中,兴奋性和抑制性神经元之间的靶向连接
支持持续的活动和竞争的行动选择。建议的测试方法
这个假设是测量和操纵老鼠的神经活动,
听觉和视觉刺激的决定。三种方法合在一起构成了
评估这一假设的建议,并提供一个新的观点决策电路。
首先,听觉和视觉决定激活重叠或基本分离的程度
神经结构将基于在脑缺血期间的全皮层活动的宽视野成像来评估。
决策的将在表达钙离子的转基因小鼠中测量全皮质活性。
皮质兴奋性神经元的指标。我们将使用的分类器和决策模型
将大脑结构中的活动与决策计算联系起来。这种方法将
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学抑制将用于评估它们的因果关系。
在决策中的作用。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的影响,例如事件
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关系的区域
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的群体成像。实验
受试者将是转基因小鼠,其中抑制性神经元发出红色荧光,
独立于用作神经活动估计的绿色荧光。这两
分离的信号使得区分兴奋性神经元和抑制性神经元成为可能,
各自在决策中的作用。单次试验分类器将用于评估
兴奋性和抑制性群体预测动物选择的能力。这场
实验将被用来区分候选模型的决策。
英文摘要
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.
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