SYNAPTIC COMPUTATIONS IN CENTRAL VESTIBULAR NEURONS

Project summary Brainstem vestibulospinal neurons receive information about head movement from vestibular afferents, but for unexplained reasons, during locomotion they also receive a copy of motor commands, in the form of a rhythmic oscillation aligned with the locomotor cycle. It is unknown whether the job of this locomotor copy, known as a corollary discharge, is to cancel the expected head movement information—thereby allowing vestibulospinal neurons to focus on encoding unexpected head movements—or to enhance expected head movement information, reducing the error inherent in sensory signals. Furthermore, the circuits that give rise to this corollary discharge are undefined. Because other brainstem neurons, like reticulospinal neurons, also exhibit these locomotor-driven oscillations, this corollary discharge signal is likely to be important in coordinating activity between the brainstem and spinal cord more generally. The goal of this proposal is to define the synaptic components underlying this corollary discharge, measure how sensory signals combine with corollary discharge, and identify the presynaptic sources of this signal. In addition, completion of this proposal will produce a synaptic-resolution map of the brainstem, broadly accessible to other researchers. Work will be carried out in the young zebrafish, whose transparency permits accessibility to in vivo whole-cell recordings not feasible in other vertebrates. Specific goals of this project are (1) to characterize the excitatory and inhibitory synaptic inputs underlying corollary discharge and define how they summate with sensory input; (2) to acquire and leverage connectomic data to identify candidate presynaptic partners carrying this corollary discharge signal; and (3) to determine the genetic identity and function of presynaptic inputs driving corollary discharge. This proposal relies on a combination of approaches, including whole-cell in vivo physiological recordings, anatomical and optogenetic mapping of circuitry, and serial-section electron microscopy and reconstructions. The project is conceptually innovative in that it seeks to define a larger-scale principle for ascending corollary discharge carrying specific information about the locomotor cycle. The overall contribution of this work will be to define a circuit that is widespread across vertebrates and operates at the level of coordination between the brainstem and spinal cord for effective motor control.