Greaney, M. R. | bioRxiv Science

bioRxiv2022

Neuronal birthdate reveals topography in a vestibular brainstem circuit for gaze stabilization

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Lastly, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. Collectively, we find that development reveals previously hidden organization to the input, processing, and output layers of a highly-conserved vertebrate sensorimotor circuit. The spatial and temporal attributes we uncover constrain the developmental mechanisms that may specify the fate, function, and organization of vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, temporal mechanisms may assemble vertebrate sensorimotor architecture.

neuroscience↗

bioRxiv2021

Synaptic Encoding of Vestibular Sensation Regulates Movement Timing and Coordination

Vertebrate vestibular circuits use sensory signals derived from the inner ear to guide both corrective and volitional movements. A major challenge in the neuroscience of balance is to link the synaptic and cellular substrates that encode body tilts to specific behaviors that stabilize posture and enable efficient locomotion. Here we address this problem by measuring the development, synaptic architecture, and behavioral contributions of vestibulospinal neurons in the larval zebrafish. First, we find that vestibulospinal neurons are born and are functionally mature before larvae swim freely, allowing them to act as a substrate for postural regulation. Next, we map the synaptic inputs to vestibulospinal neurons that allow them to encode posture. Further, we find that this synaptic architecture allows them to respond to linear acceleration in a directionally-tuned and utricle-dependent manner; they are thus poised to guide corrective movements. After loss of vestibulospinal neurons, larvae adopted eccentric postures with disrupted movement timing and weaker corrective kinematics. We used a generative model of swimming to demonstrate that together these disruptions can account for the increased postural variability. Finally, we observed that lesions disrupt vestibular-dependent coordination between the fins and trunk during vertical swimming, linking vestibulospinal neurons to navigation. We conclude that vestibulospinal neurons turn synaptic representations of body tilt into defined corrective behaviors and coordinated movements. As the need for stable locomotion is common and the vestibulospinal circuit is highly conserved our findings reveal general mechanisms for neuronal control of balance.

neuroscience↗