PT - JOURNAL ARTICLE AU - Hamling, Kyla R. AU - Harmon, Katherine AU - Schoppik, David TI - The Nature and Origin of Synaptic Inputs to Vestibulospinal Neurons in the Larval Zebrafish AID - 10.1523/ENEURO.0090-23.2023 DP - 2023 Jun 01 TA - eneuro PG - ENEURO.0090-23.2023 VI - 10 IP - 6 4099 - http://www.eneuro.org/content/10/6/ENEURO.0090-23.2023.short 4100 - http://www.eneuro.org/content/10/6/ENEURO.0090-23.2023.full SO - eNeuro2023 Jun 01; 10 AB - Vestibulospinal neurons integrate sensed imbalance to regulate postural reflexes. As an evolutionarily conserved neural population, understanding their synaptic and circuit-level properties can offer insight into vertebrate antigravity reflexes. Motivated by recent work, we set out to verify and extend the characterization of vestibulospinal neurons in the larval zebrafish. Using current-clamp recordings together with stimulation, we observed that larval zebrafish vestibulospinal neurons are silent at rest, yet capable of sustained spiking following depolarization. Neurons responded systematically to a vestibular stimulus (translation in the dark); responses were abolished after chronic or acute loss of the utricular otolith. Voltage-clamp recordings at rest revealed strong excitatory inputs with a characteristic multimodal distribution of amplitudes, as well as strong inhibitory inputs. Excitatory inputs within a particular mode (amplitude range) routinely violated refractory period criteria and exhibited complex sensory tuning, suggesting a nonunitary origin. Next, using a unilateral loss-of-function approach, we characterized the source of vestibular inputs to vestibulospinal neurons from each ear. We observed systematic loss of high-amplitude excitatory inputs after utricular lesions ipsilateral, but not contralateral, to the recorded vestibulospinal neuron. In contrast, while some neurons had decreased inhibitory inputs after either ipsilateral or contralateral lesions, there were no systematic changes across the population of recorded neurons. We conclude that imbalance sensed by the utricular otolith shapes the responses of larval zebrafish vestibulospinal neurons through both excitatory and inhibitory inputs. Our findings expand our understanding of how a vertebrate model, the larval zebrafish, might use vestibulospinal input to stabilize posture. More broadly, when compared with recordings in other vertebrates, our data speak to conserved origins of vestibulospinal synaptic input.