Mapping superior colliculus contributions to action selection and movement

绘制上丘对动作选择和运动的贡献

• 批准号: 10349511
• 负责人: Alyse Marian Thomas
• 金额: $ 11.02万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10349511
• 关键词: Address; Animals; Attentional deficit; Basal Ganglia; Behavior; Behavior Control; Behavioral; Biological; Brain; Brain Stem; Brain region; Cell Nucleus; Cervical; Cognition Disorders; Cognitive; Contralateral; Data; Decision Making; Discrimination; Disease; Dissection; Electrodes; Electrophysiology (science); Feedback; Fostering; Foundations; Functional disorder; Goals; Health; Human; Hyperactivity; Impaired cognition; Impairment; Investigation; Knowledge; Left; Light; Link; Literature; Maps; Measures; Mediating; Mental disorders; Modeling; Modernization; Motor; Movement; Mus; Neurons; Neurosciences; Output; Parkinson Disease; Pathologic; Pathway interactions; Population; Process; Property; Ramp; Reporting; Research; Role; Structure; Techniques; Testing; Thalamic structure; Training; Transgenic Mice; Virus; Work; base; behavioral response; career; cell type; cognitive control; daily functioning; density; excitatory neuron; experimental study; frontal lobe; inhibitory neuron; motor control; motor disorder; motor impairment; nervous system disorder; neural correlate; neuromechanism; optogenetics; relating to nervous system; response; segregation; somatosensory; superior colliculus Corpora quadrigemina; theories

Optimal behavioral responses require decision-making and motor control. Deficits in action selection are associated with motor disorders, pathological behaviors, and cognitive dysfunction. A neural correlate of action selection has been observed in the sustained ramping of movement-selective neurons across multiple brain regions, suggesting a distributed neural mechanism. Though interactions between frontal cortex (FC) and basal ganglia (BG) are traditionally thought to mediate action selection, recent data suggests that subcortical motor structures like the superior colliculus (SC) can also bias upcoming behaviors. The SC is reciprocally connected with FC and BG via motor thalamus, forming a loop-like circuit. Yet, it remains unknown how SC influences activity in FC and BG, nor is clear how SC participates in action selection without evoking movement. The goal of this proposal is to map SC contributions to action selection and movement using a delayed-response sensorimotor discrimination task in mice. Based on previous literature and preliminary findings, it is hypothesized that the SC drives motor representations in FC and BG to bias decision-making. Spatially and temporally precise optogenetic perturbation will be combined with multi-electrode recording in behaving animals to evaluate a causal role of collicular activity across a multi-regional circuit. Transient perturbations in SC will be combined with high-density recordings in FC and BG. Next motor representations in SC will be mapped onto local excitatory and inhibitory neurons. Finally, divergent collicular output pathways will be dissected for their respective role in selection versus movement. My preliminary data reveal the segregation SC output neurons projecting to thalamus (implicated in action selection) versus brainstem (implicated in movement). Projection-specific tagging will reveal the electrophysiological properties of these separate populations during behavior. In addition, projection-specific manipulation will demonstrate their distinct roles in selection versus movement. Taken together, these experiments will shed light on the neural mechanisms of distributed action selection dynamics and map action representations in SC onto discrete cell-types and projections. In addition to implicating subcortical motor structures in cognitive control, these results will provide a foundation for circuit-based investigation into cognitive- and motor-related neurological disorders.

最佳行为反应需要决策和运动控制。动作选择中的缺陷与运动障碍，病理行为和认知功能障碍有关。在多个大脑区域的运动选择性神经元的持续渐变中观察到了动作选择的神经相关性，这表明有分布式神经机制。尽管传统上认为额叶皮层（FC）和基底神经节（BG）之间的相互作用可以介导作用选择，但最近的数据表明，皮层运动结构（例如上丘脑（SC））也可以偏向即将发生的行为。 SC通过电动机丘脑与FC和BG相互连接，形成一个环状电路。然而，SC仍然未知如何影响FC和BG的活动，也不清楚SC在不引起运动的情况下参与行动选择。该提案的目的是使用小鼠中的延迟反应感觉运动歧视任务对行动选择和运动进行映射。根据以前的文献和初步发现，假设SC将FC和BG中的运动表示驱动到偏置决策。在空间和时间上精确的光遗传学扰动将与行为动物中的多电极记录相结合，以评估跨多区域电路的碰撞活性的因果作用。 SC中的瞬态扰动将与FC和BG中的高密度记录结合使用。 SC中的下一个运动表示将映射到局部兴奋性和抑制性神经元上。最后，将阐述发散的胶状输出途径，以在选择与运动中各自的作用。我的初步数据揭示了投射到丘脑的隔离SC输出神经元（与动作选择有关）与脑干（与运动有关）。投影特异性标签将揭示行为过程中这些独立人群的电生理特性。此外，投影特定的操作将证明它们在选择与运动中的独特作用。综上所述，这些实验将阐明分布式动作选择动力学的神经机制和SC中的MAP动作表示形式对离散的细胞类型和投影。除了将皮层运动结构与认知控制中相关，这些结果还将为基于电路的认知和运动相关神经系统疾病的研究提供基础。