Neural circuit mechanisms underlying cognitive control of sensory-guided behavior

感觉引导行为认知控制的神经回路机制

• 批准号: 9176955
• 负责人: David J Margolis
• 金额: $ 33.91万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9176955
• 关键词: Address; Apical; Area; Axon; Basal Ganglia; Behavior; Behavior Control; Behavioral; Behavioral inhibition; Brain; Calcium; Chronic; Cognitive; Corpus striatum structure; Data; Dendrites; Development; Discrimination; Dorsal; Electrophysiology (science); Etiology; Feedback; Functional disorder; Gilles de la Tourette syndrome; Goals; Head; Huntington Disease; Image; Impulsive Behavior; Impulsivity; Knowledge; Label; Learning; Measurement; Methods; Mus; Neurons; Obsessive-Compulsive Disorder; Output; Pathway interactions; Performance; Population; Prefrontal Cortex; Probability; Process; Research; Response to stimulus physiology; Reversal Learning; Role; Sensory; Series; Signal Transduction; Somatosensory Cortex; Stimulus; Tactile; Task Performances; Testing; Texture; Therapeutic; Time; Vibrissae; base; behavior influence; behavioral response; calcium indicator; cellular imaging; cognitive control; frontal lobe; improved; in vivo; integration site; motor control; nervous system disorder; neural circuit; neuronal cell body; neuronal circuitry; neurotransmission; novel; optogenetics; recombinase; relating to nervous system; research study; response; sensory cortex; sensory stimulus; treatment strategy; two-photon

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.

概括 反应抑制，在适当情况下抑制行动的能力对于认知很重要 对行为及其功能障碍的控制已与许多神经系统疾病有关。这个建议 旨在了解性能过程中小鼠的基础抑制抑制皮质纹状体信号传导和 学习基于晶须的触觉歧视任务。一个主要目标是解决知识的差距 存在原发性体感皮质（S1）在响应抑制中的作用。基于其突出的 对纹状体的预测和越来越多的感觉运动功能，S1是被忽视的候选人 与额叶大脑相比，在行为控制中的大脑刺激 区域。提出的实验首先旨在建立S1皮质输入之间的因果关系 和行为任务表现。假设是通过其从S1到背纹状体（DSTR）的信号传导。 大量的轴突投影是必要的，足以驱动行为反应和反应抑制 适当的行为环境。我们将通过表达光遗传执行器和 S1中的消音器（CHR2，ARCHT），并在任务执行过程中操纵DSTR中的轴突活动。结果 将建立S1对感觉引导行为的因果影响。下一个系列实验将 使用慢性体内两光子成像和 电生理学。遗传编码的钙指标的慢性成像将允许成像深 S1中的层纹状体投影神经元，以确定S1-DSTR群体的行为选择性。这 假设是S1-DSTR神经元的亚群，分别编码反应激活和抑制作用。 与行为相关的神经元活性的时机将使用靶向电生理记录解决。 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 使用慢性两光子成像在S1中的活性变化。实验将通过初始进行 学习和刺激逆转以解离刺激和反应。我们的实验方法将提供 有关S1-DSTR预测能力引发响应抑制的能力的关键信息，这将具有 改善涉及认知/行为控制缺陷的神经系统疾病的治疗的影响。