Wednesday, April 30, 2025
4/30/2025
Spatiotemporal encoding of goal-directed reaching across early cerebellar circuitry - PROJECT SUMMARY/ABSTRACT Many fundamental aspects of our lives heavily rely on an intact motor system: we need it to explore, to communicate, to interact with our surroundings. The cerebellum is uniquely involved in reach dysmetria, whereby the limb oscillates about an end target, resulting in diminished reach precision. Though our ability to make precise, goal-directed movements is so critical, we still lack a complete understanding of how the brain generates the appropriate activity to achieve something as simple as reaching for a coffee cup. Fortunately, the cerebellar circuitry is uniquely organized and well-defined; this lends itself to being a tractable structure for testing theoretical models of its computational logic in practice with the advent of updated neuroscientific tools. Two such models that describe how the cerebellar cortex guides endpoint precision in reaching are that it 1) integrates limb velocity to estimate positional values or that it 2) recodes sensorimotor information into temporally distinct activity patterns. To investigate the computational logic the cerebellum engages to enable goal-directed reaching, I will use two-photon calcium imaging to measure activity in early cerebellar cortex during a multi-target reach task in mice. In Aim 1, I will image granule cell axons and molecular layer interneurons to test the hypothesis that information about target location and movement goal is relayed to the cerebellar cortex by its mossy fiber inputs. I will leverage multi-view, high-resolution video, supervised body part tracking, and multi- photon imaging to identify how location and limb velocity information content is encoded by granule cells. In Aim 2, I will use targeted photoexcitation of mossy fiber inputs to induce motor adaptation to test the hypothesis that stimulation results in a misrepresentation of sensory estimates in granule cells, which drives errant reaching behavior, and adaptation to the perturbation is a resultant of a re-mapping of the new information content. Collectively, these data will distinguish whether the cerebellar cortex computes a control function or temporal basis set model to guide endpoint precision. By rigorously evaluating behavioral motor motifs in rodent models and linking these to neuronal activity, we can gain clarity into how discrete actions lead to overall performance and open up more possibilities to better addressing fundamental questions relating to the neural mechanisms of motor control and learning.
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