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。在多个大脑区域的运动选择性神经元的持续增强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。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调节动作选择，但最近的数据表明，上丘 (SC) 等皮层下运动结构也可以使即将发生的行为产生偏差。 SC通过运动丘脑与FC、BG相互连接，形成环状电路。然而，尚不清楚 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。该提案的目标是利用小鼠的延迟反应感觉运动辨别任务来绘制 SC 对动作选择和运动的贡献。根据之前的文献和初步研究结果，假设 SC 驱动 FC 和 BG 中的运动表征，从而使决策产生偏差。空间和时间上精确的光遗传学扰动将与行为动物的多电极记录相结合，以评估跨多区域回路的丘脑活动的因果作用。 SC 中的瞬态扰动将与 FC 和 BG 中的高密度记录相结合。 SC 中的下一步运动表征将被映射到局部兴奋性和抑制性神经元上。最后，将剖析不同的丘脑输出路径，以确定它们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（涉及动作选择）与脑干（涉及运动）的分离 SC 输出神经元。投影特异性标记将揭示这些不同群体在行为过程中的电生理特性。此外，特定于投影的操作将展示它们在选择与移动中的独特作用。总而言之，这些实验将揭示分布式动作选择动力学的神经机制，并将 SC 中的动作表征映射到离散的细胞类型和预测上。除了在认知控制中暗示皮层下运动结构之外，这些结果还将为基于回路的认知和运动相关神经系统疾病的研究提供基础。

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.