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、病理性行为和认知功能障碍有关。在跨越多个脑区的运动选择神经元的持续倾斜中观察到了动作选择的神经关联，表明了一种分布式神经机制。虽然额叶皮质(FC)和基底节(BG)之间的相互作用传统上被认为是调节动作选择的，但最近的数据表明，皮质下运动结构如上丘(SC)也可以偏向即将到来的行为。SC通过丘脑运动与FC、BG相互连接，形成环状回路。然而，SC如何影响Fc和BG中的活动，也不清楚SC如何在不引起运动的情况下参与动作选择，目前还不清楚。这项建议的目的是利用小鼠的延迟反应感觉运动辨别任务来定位SC对动作选择和运动的贡献。根据以前的文献和初步的研究结果，假设SC驱动FC和BG中的运动表征来偏向决策。空间和时间上精确的光遗传微扰将与动物行为的多电极记录相结合，以评估跨多区域环路的丘脑活动的因果作用。SC中的瞬时扰动将与FC和BG中的高密度记录结合在一起。下一步，SC中的运动表征将被映射到局部的兴奋性和抑制性神经元。最后，将解剖不同的丘输出通路，以了解它们在选择和运动中各自所起的作用。我的初步数据显示，分离的SC输出神经元投射到丘脑(与动作选择有关)与脑干(与运动有关)。投射特异性标记将揭示这些不同种群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和移动中的不同角色。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，并将SC中的动作表征映射到离散的细胞类型和投影上。除了在认知控制中涉及皮质下运动结构，这些结果还将为认知和运动相关神经障碍的基于电路的研究提供基础。

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.