The ability to appropriately interact with the environment is fundamental to an animal's survival, and a network of interconnected brain regions subserves this purpose. When a part of this network goes awry, such as the basal ganglia in Parkinson's disease, quality of life decreases and so does survival. The superior colliculus (SC) is a highly conserved midbrain structure that works in this network as a sensorimotor hub to guide attention and movements toward salient environmental stimuli, an essential survival behavior for identifying food and foe. In this network, the SC presumably transforms sensory and cortical information (e.g., sights and sounds, motivational state) into action (i.e., movement initiation); however, due to the tangle of cell types and projections to, within and from the SC, current approaches have been unable to determine how this transformation is accomplished. This proposal aims to uncover the functional circuitry underlying goal-directed behaviors by examining the intra-SC dynamics that guide these behaviors. The experiments proposed are motivated by the synthesis of behavioral and slice physiology studies that together demonstrate a functional organization in the SC. The SC is organized along the horizontal axis to direct behavior to contralateral space so that, for example, movement to rightward space is directed by the left SC. The focus of this proposal is on the integrative and motor output properties of the intermediate and deep layers of the SC. Here, two specific SC populations will be recorded from and manipulated during behavior.
The first Aim will address how SC premotor output neuron location within the SC influences the type of movement executed. This will be accomplished using a dual-virus method to restrict channelrhodopsin (ChR2) to a specific population of SC premotor output neurons in a cohort of animals trained on a sensorimotor task. These premotor output neurons can then be tracked throughout behavior to identify precisely when they are active and also optically activated to determine how these premotor output neurons drive behavior.
The second Aim will investigate the role of SC inhibitory neurons by implementing similar methods, with the hypothesis that their activity influences the selection of behaviorally relevant stimuli. The results acquired from these experiments will inform models for how neural circuits mediate behavior and also inform how similar circuits can be repaired therapeutically in motor pathologies.

Public Health Relevance

Behavior is controlled by an interconnected network of brain regions, but how activity in these regions is translated to produce appropriate behavior (e.g., approach vs escape) is poorly understood. The superior colliculus (SC) is central in this network for mediating goal-directed behaviors, however it is unclear how the functional circuitry in the SC subserves this purpose. This proposal aims to elucidate how two key cell populations in the SC contribute to guiding goal-directed behaviors under normal conditions, which can ultimately inform motor pathologies.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1)
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Chen, Daofen
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University of Colorado Denver
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United States
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