Mapping superior colliculus contributions to action selection and movement

最佳的行为反应需要决策和运动控制。动作选择缺陷与运动障碍、病理行为和认知功能障碍有关。在多个脑区的运动选择神经元的持续斜坡中观察到了动作选择的神经相关性，这表明了分布式神经机制。虽然传统上认为额叶皮层（FC）和基底神经节（BG）之间的相互作用介导的动作选择，最近的数据表明，皮质下运动结构，如上级丘（SC）也可以偏见即将到来的行为。SC通过运动丘脑与FC和BG相连，形成环状回路。然而，它仍然是未知的SC如何影响FC和BG的活动，也不清楚SC如何参与动作选择而不引起运动。这项建议的目标是映射SC的贡献，动作选择和运动使用延迟响应感觉运动的歧视任务小鼠。基于先前的文献和初步研究结果，我们假设SC驱动FC和BG中的运动表征以使决策产生偏差。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，以评估跨多区域回路的丘活动的因果作用。SC中的瞬时扰动将与FC和BG中的高密度记录相结合。接下来，SC中的运动表征将被映射到局部兴奋性和抑制性神经元。最后，不同的丘输出通路将解剖其各自的作用，选择与运动。我的初步数据显示分离SC输出神经元投射到丘脑（涉及动作选择）与脑干（涉及运动）。投射特异性标记将揭示这些单独种群在行为过程中的电生理特性。此外，投射特定的操纵将展示它们在选择与运动中的不同作用。两者合计，这些实验将揭示分布式动作选择动态和地图上的动作表示SC到离散的细胞类型和预测的神经机制。除了涉及认知控制皮层下运动结构，这些结果将提供一个基于电路的调查认知和运动相关的神经系统疾病的基础。

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.