Multiple circuits controlling the versatility of locomotion : molecular and connectivity principles in zebrafish

Abstract

Locomotion is produced by neuronal circuits in the spinal cord. These motor circuits rely on the activation of supraspinal centres and transform descending excitatory drive into coordinated rhythmic activity. Far from generating a mere stereotyped behaviour, the spinal locomotor circuit is endowed with mechanisms that allow for flexible motor output with appropriate changes in speed and strength to match specific external and internal demands. These mechanisms are not cemented after the initial assembly of the circuits at early developmental stages but face the necessity to adapt during maturation to the new behavioural needs of the animal. In this thesis, we take advantage of the genetic and experimental accessibility of the adult zebrafish as a model system to study the detailed organization of the spinal motor circuits that underlies the versatility of locomotion.

In adult zebrafish, the spinal locomotor circuit does not consist of a single network, but is modular, and comprises three types of rhythm-generating excitatory V2a interneurons (INs) that connect selectively to motoneurons (MNs) innervating the slow, intermediate or fast muscle fibers. The three V2a IN-MN circuit modules are recruited sequentially to drive swimming at different speeds. In the first study presented in this thesis, we reveal how the connectivity pattern of V2a INs, together with their intrinsic pacemaker properties, enables the initiation of rhythmic locomotion and allows for smooth transitions in speed. In the second study, we explore how the connectivity and function of the earliest-born V2a INs and primary MNs (pMNs) change during maturation from larval to adult stages. As the swimming behaviour shifts to lower frequencies in adult zebrafish, neurons that are involved in generating locomotion at fast speeds in larvae become embedded in different circuits and are redeployed to new functions. Finally in the third study included in this thesis, we reveal the molecular logic underpinning the diversity of MNs and V2a INs and their organization into three speed circuit modules. Overall, this work expands our knowledge of the molecular and functional organization of the spinal motor circuits, uncovering general principles that could be conserved in other vertebrate species.