Investigating Cerebellotectal projections in target acquisition

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PROJECT SUMMARY How the nervous system acquires targets (i.e. the ability to move to and stop precisely at a target) with such incredible precision is a fundamental question of motor control and systems neuroscience. A network of several brain regions is implicated in these processes, but how activity is coordinated across structures and cell types is unknown. In particular, the reciprocally-interconnected superior colliculus (SC) and cerebellum (Cb) are two major hubs of this network: The deep layers of the SC contain a topographic map in which the eccentricity of a contralateral spatial target is represented by the location of activity along its rostrocaudal axis, with the rostral pole reflecting target acquisition; the Cb, by contrast, refines movements by providing feedforward control signals based on learned associations. While previous investigations have shown the Cb and SC share complementary roles in orienting behaviors, the nature of their interaction in controlling movement for target acquisition is unclear. Cerebellotectal projections, afferent projections from cerebellar nuclei (CbNs) to excitatory neurons in the rostral SC, are ideally situated to control precise target acquisition. However, previous manipulations of cerebellotectal projections and SC target neurons have been limited, used reversible lesions that lasted much longer than a single movement, and lacked cell-type specificity, preventing any causal test of whether cerebellar output to the superior colliculus functions to enhance precision in target acquisition. To address these limitations, this proposal utilizes a closed-loop behavioral system for mice in which optogenetic manipulation is triggered by the real-time kinematics of precise orienting limb movements for target acquisition. Combining this system with optogenetic control of CbN neurons and cell-type specific opsin expression in excitatory SC neurons will allow for short-term reversible manipulation of cerebellar output and excitatory SC activity at specific kinematic locations of precise orienting movements, directly interrogating the role of cerebellar contribution to the superior colliculus in controlling precise target acquisition.