Motor neurons control locomotor circuit function retrogradely via gap junctions.

Motor neurons are the final stage of neural processing for the execution of motor behaviours. Traditionally, motor neurons have been viewed as the 'final common pathway', serving as passive recipients merely conveying to the muscles the final motor program generated by upstream interneuron circuits. Here we reveal an unforeseen role of motor neurons in controlling the locomotor circuit function via gap junctions in zebrafish. These gap junctions mediate a retrograde analogue propagation of voltage fluctuations from motor neurons to control the synaptic release and recruitment of the upstream V2a interneurons that drive locomotion. Selective inhibition of motor neurons during ongoing locomotion de-recruits V2a interneurons and strongly influences locomotor circuit function. Rather than acting as separate units, gap junctions unite motor neurons and V2a interneurons into functional ensembles endowed with a retrograde analogue computation essential for locomotor rhythm generation. These results show that motor neurons are not a passive recipient of motor commands but an integral component of the neural circuits responsible for motor behaviour.

Developmental switch in the function of inhibitory commissural V0d interneurons in zebrafish.

During development, all animals undergo major adaptations to accommodate behavioral flexibility and diversity. How these adaptations are reflected in the changes in the motor circuits controlling our behaviors remains poorly understood. Here, we show, using a combination of techniques applied at larval and adult zebrafish stages, that the pattern-generating V0d inhibitory interneurons within the locomotor circuit undergo a developmental switch in their role. In larvae, we show that V0d interneurons have a primary function in high-speed motor behavior yet are redundant for explorative swimming. By contrast, adult V0d interneurons have diversified into speed-dependent subclasses, with an overrepresentation of those active at the slowest speeds. The ablation of V0d interneurons in adults disrupts slow explorative swimming, which is associated with a loss of mid-cycle inhibition onto target motoneurons. Thus, we reveal a developmental switch in V0d interneuron function from a role in high-speed motor behavior to a function in timing and thus coordinating slow explorative locomotion. Our study suggests that early motor circuit composition is not predictive of the adult system but instead undergoes major functional transformations during development.

A spinal organ of proprioception for integrated motor action feedback.

Proprioception is essential for behavior and provides a sense of our body movements in physical space. Proprioceptor organs are thought to be only in the periphery. Whether the central nervous system can intrinsically sense its own movement remains unclear. Here we identify a segmental organ of proprioception in the adult zebrafish spinal cord, which is embedded by intraspinal mechanosensory neurons expressing Piezo2 channels. These cells are late-born, inhibitory, commissural neurons with unique molecular and physiological profiles reflecting a dual sensory and motor function. The central proprioceptive organ locally detects lateral body movements during locomotion and provides direct inhibitory feedback onto rhythm-generating interneurons responsible for the central motor program. This dynamically aligns central pattern generation with movement outcome for efficient locomotion. Our results demonstrate that a central proprioceptive organ monitors self-movement using hybrid neurons that merge sensory and motor entities into a unified network.

Principles Governing Locomotion in Vertebrates: Lessons From Zebrafish.

Locomotor behaviors are critical for survival and enable animals to navigate their environment, find food and evade predators. The circuits in the brain and spinal cord that initiate and maintain such different modes of locomotion in vertebrates have been studied in numerous species for over a century. In recent decades, the zebrafish has emerged as one of the main model systems for the study of locomotion, owing to its experimental amenability, and work in zebrafish has revealed numerous new insights into locomotor circuit function. Here, we review the literature that has led to our current understanding of the neural circuits controlling swimming and escape in zebrafish. We highlight recent studies that have enriched our comprehension of key topics, such as the interactions between premotor excitatory interneurons (INs) and motoneurons (MNs), supraspinal and spinal circuits that coordinate escape maneuvers, and developmental changes in overall circuit composition. We also discuss roles for neuromodulators and sensory inputs in modifying the relative strengths of constituent circuit components to provide flexibility in zebrafish behavior, allowing the animal to accommodate changes in the environment. We aim to provide a coherent framework for understanding the circuitry in the brain and spinal cord of zebrafish that allows the animal to flexibly transition between different speeds, and modes, of locomotion.

Functional diversity of excitatory commissural interneurons in adult zebrafish.

Flexibility in the bilateral coordination of muscle contraction underpins variable locomotor movements or gaits. While the locomotor rhythm is generated by ipsilateral excitatory interneurons, less is known about the commissural excitatory interneurons. Here we examined how the activity of the V0v interneurons - an important commissural neuronal class - varies with the locomotor speed in adult zebrafish. Although V0v interneurons are molecularly homogenous, their activity pattern during locomotion is not uniform. They consist of two distinct types dependent on whether they display rhythmicity or not during locomotion. The rhythmic V0v interneurons were further subdivided into three sub-classes engaged sequentially, first at slow then intermediate and finally fast locomotor speeds. Their order of recruitment is defined by scaling their synaptic current with their input resistance. Thus we uncover, in an adult vertebrate, a novel organizational principle for a key class of commissural interneurons and their recruitment pattern as a function of locomotor speed.

Long-lasting effects of chemical hypoxia on spinal cord function in tadpoles.

We investigated the effects of chemical hypoxia on the central pattern generator controlling swimming in stage 42 Xenopus laevis larvae. We recorded motoneuron activity from ventral roots of immobilized tadpoles and evoked swim episodes by brief electrical stimulation of the tail skin. In the presence of the metabolic inhibitor, sodium azide (5 mM, NaN3), swim episode duration and cycle frequency decreased until swim motor patterns could not be evoked. On recovery, cycle frequency returned to preazide levels; however, episode duration remained short for at least an hour. In addition, recovery induced spontaneous, short bouts of swimming similar to the slow rhythm that is evoked by N-methyl-D-aspartic acid. We conclude that abiotic features of the environment can have long-term modulatory effects on circuit function in the CNS.