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.
Deficits in the decision-making and movement are associated with severe neurological disorders, significantly impairing daily function in human populations. The frontal cortex, basal ganglia, and superior colliculus are interconnected, and each brain region has separately been implicated in behavioral control. This proposal aims to dissect multi-regional interactions in order to foster a circuit-based understanding of behavior under conditions of health and disease.
