Principles of sensorimotor processing in zebrafish thermosensation

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SUMMARY It is our long-term goal to understand computations that underlie sensori-motor transformations in the context of thermoregulatory behaviors. Generating appropriate behaviors in response to sensory stimuli is critical for the survival of any animal. Larval zebrafish will be used for these studies as it is the only vertebrate model which allows comprehensive identification and manipulation of thermoregulatory circuits. Importantly, larval zebrafish is an ectotherm animal and therefore exclusively relies on thermal gradient navigation for thermoregulation. This means that the underlying sensori-motor transformations are robust since accurate thermoregulation is critical for survival. The accessibility of the zebrafish nervous system to optical recording of neural activity enabled us to map thermoregulatory circuits from sensory input to behavioral output for the first time in any animal. This research identified two critical classes of hindbrain neurons which encode the rate of heating and the rate of cooling in the environment. Notably, these heating and cooling responses are computed de-novo in the hindbrain from sensory trigeminal inputs. The aim of this proposal is to uncover the biophysical mechanism of these computations and their role in behavior generation to generate a multiscale model of sensori-motor transformations. The proposed experiments are guided by testable hypotheses about hindbrain computation that are based on our previous circuit modeling efforts. Specifically, the research will investigate the (1) cellular mechanisms of computing heating and cooling responses, (2) how the circuit anatomy supports this computation and (3) how the responses of Heating and Cooling neurons influence turning during thermoregulatory behavior. To this end experiments will combine (1) patch electrophysiology in functionally identified neurons, (2) single cell labeling through electroporations and (3) cell type specific ablations followed by behavioral recordings. This research will fill a critical gap in our understanding of sensori-motor transformations: How computations at different scales, from cellular properties to circuits, interact to generate adaptive behaviors in response to sensory stimuli. The understanding of conserved and divergent principles of sensori-motor transformations across animals and sensory modalities furthermore promises insight into what goes awry in neurological disease states where sensory processing goes awry.