Mechanosensory neurons control the timing of spinal microcircuit selection during locomotion.

Despite numerous physiological studies about reflexes in the spinal cord, the contribution of mechanosensory feedback to active locomotion and the nature of underlying spinal circuits remains elusive. Here we investigate how mechanosensory feedback shapes active locomotion in a genetic model organism exhibiting simple locomotion-the zebrafish larva. We show that mechanosensory feedback enhances the recruitment of motor pools during active locomotion. Furthermore, we demonstrate that inputs from mechanosensory neurons increase locomotor speed by prolonging fast swimming at the expense of slow swimming during stereotyped acoustic escape responses. This effect could be mediated by distinct mechanosensory neurons. In the spinal cord, we show that connections compatible with monosynaptic inputs from mechanosensory Rohon-Beard neurons onto ipsilateral V2a interneurons selectively recruited at high speed can contribute to the observed enhancement of speed. Altogether, our study reveals the basic principles and a circuit diagram enabling speed modulation by mechanosensory feedback in the vertebrate spinal cord.

Intraspinal Sensory Neurons Provide Powerful Inhibition to Motor Circuits Ensuring Postural Control during Locomotion.

In the vertebrate spinal cord, cerebrospinal fluid-contacting neurons (CSF-cNs) are GABAergic neurons whose functions are only beginning to unfold. Recent evidence indicates that CSF-cNs detect local spinal bending and relay this mechanosensory feedback information to motor circuits, yet many CSF-cN targets remain unknown. Using optogenetics, patterned illumination, and in vivo electrophysiology, we show here that CSF-cNs provide somatic inhibition to fast motor neurons and excitatory sensory interneurons involved in the escape circuit. Ventral CSF-cNs respond to longitudinal spinal contractions and induce large inhibitory postsynaptic currents (IPSCs) sufficient to silence spiking of their targets. Upon repetitive stimulation, these IPSCs promptly depress, enabling the mechanosensory response to the first bend to be the most effective. When CSF-cNs are silenced, postural control is compromised, resulting in rollovers during escapes. Altogether, our data demonstrate how GABAergic sensory neurons provide powerful inhibitory feedback to the escape circuit to maintain balance during active locomotion.