Neural circuit mechanisms underlying cognitive control of sensory-guided behavior

总结 反应抑制，即在适当的语境中抑制行为的能力，对认知过程很重要。 行为控制及其功能障碍与许多神经障碍有关。这项建议 旨在了解小鼠在表现过程中皮质纹状体信号传导的潜在反应抑制， 学习基于胡须的触觉辨别任务。一个主要目标是解决知识上的差距， 存在初级躯体感觉皮层（S1）在反应抑制中的作用。基于其突出的 S1是一个被忽视的候选者， 在行为控制方面的脑刺激，与额叶相比， 地区所提出的实验首先旨在建立来自S1的皮层输入之间的因果关系 和行为任务表现。假设从S1到背侧纹状体（DStr）的信号，通过其 大量的轴突投射，是必要的，足以驱动行为反应和反应抑制， 适当的行为背景。我们将通过表达光遗传学致动器来测试这一假设， 沉默剂（ChR 2，ArchT）在S1和操纵轴突活动的DStr在任务的执行。结果 将确定S1对感觉引导行为的因果影响。接下来的一系列实验将 使用慢性体内双光子成像研究S1中任务相关活动的细胞基础， 电生理学遗传编码钙指标的慢性成像将允许对深部 S1层纹状体投射神经元，以确定S1-DStr群体的行为选择性。的 假设S1-DStr神经元亚群分别编码反应激活和抑制。 将使用靶向电生理记录来解析行为相关神经元活动的时间。 最后一系列的实验将通过跟踪确定细胞行为选择性的出现 使用慢性双光子成像的S1的活性变化。实验将通过初始 学习和刺激逆转，以分离刺激和反应。我们的实验方法将提供 关于S1-DStr预测引起反应抑制的能力的关键信息， 对改善涉及认知/行为控制缺陷的神经系统疾病的治疗的意义。

SUMMARY Response inhibition, the ability to inhibit actions in the appropriate contexts, is important for the cognitive control of behavior and its dysfunction has been implicated in numerous neurological disorders. This proposal aims to understand corticostriatal signaling underlying response inhibition in mice during performance and learning of a whisker-based tactile discrimination task. A major goal is to address the gap in knowledge that exists for the role of primary somatosensory cortex (S1) in response inhibition. Based on its prominent projections to striatum and increasingly appreciated sensorimotor functionality, S1 is an overlooked candidate for brain stimulation in behavioral control that could have therapeutic advantages compared to frontal brain areas. The proposed experiments first aim to establish a causal relationship between cortical input from S1 and behavioral task performance. The hypothesis is that signaling from S1 to dorsal striatum (DStr), via its massive axonal projection, is necessary and sufficient to drive behavioral responses and response inhibition in the appropriate behavioral context. We will test this hypothesis by expressing optogenetic actuators and silencers (ChR2, ArchT) in S1 and manipulating axonal activity in DStr during task performance. The results will establish the causal influence of S1 on sensory-guided behavior. The next series of experiments will investigate the cellular basis of task-related activity in S1 using chronic in vivo two-photon imaging and electrophysiology. Chronic imaging of genetically encoded calcium indicators will allow for imaging of deep layer striatal projection neurons in S1 to determine the behavioral selectivity of S1-DStr populations. The hypothesis is that subpopulations of S1-DStr neurons encode response activation and inhibition, respectively. The timing of behavior-related neuronal activity will be resolved using targeted electrophysiological recordings. The final series of experiments will determine the emergence of cellular behavioral selectivity by tracking activity changes in S1 using chronic two-photon imaging. Experiments will be performed both through initial learning and stimulus reversal to dissociate stimulus and response. Our experimental approach will provide critical information about the capacity of S1-DStr projections for eliciting response inhibition, which will have implications for improved treatment of neurological disorders involving deficits in cognitive/behavioral control.