RETICULOSPINAL NEURONS IN MOTOR CONTROL – MotorV2

This project aims at deciphering the function of genetically-defined groups of neurons in the central nervous system, with cutting edge tools that are increasingly applied to interrogate the neuronal basis of behavior. More specifically, it will explore clusters of brainstem neurons in motor control. The project finds its roots in my previous work on the locomotor behavior and its supra-spinal control.

We will focus in particular on one genetically-identified class of brainstem neurons that recapitulates the majority of glutamatergic reticulospinal neurons and was recently shown to either stop ongoing locomotion, that may induce locomotion or that can accelerate breathing. This sets the stage for investigating further the diversity within this neuronal population and its articulation with mutually exclusive roles in locomotor initiation and termination or with synergistic controls of locomotion and breathing. The methodology will imprint from developmental biology to manipulate homogenous cell types on the basis of their shared history of expression of developmental genes, and use cutting-edge viral tracings and optogenetics in vitro and in vivo.

We will perform on the one hand a piece-meal circuit deciphering of the neuronal inputs onto spatially-confined subsets of these genetically-defined RS neurons as a proxy of the relevant contexts for mobilizing them. Altogether, this will provide identification of structures involved in the planning/motivation of movements. We will also consider, as prompted by my preliminary observations, that the same RS neurons that arrest locomotion might co-modulate breathing, another essential motor behavior linked to locomotion in the context of exercise or exploratory tasks and defensive responses. We will therefore characterize neurons interfacing two essential motor behavior, and thus explore the multimodal function of the brainstem reticular formation. We will similarly explore the possibility that spatially-confined subsets of RS neurons of a common genetic origin are dedicated to control the initiation versus termination of the locomotor behavior. This will inform on the intrinsic building logic of functional modules within the reticular formation and will be relevant for the supra-spinal gating of the locomotor behavior. We will finally reveal the identities of cell types, within the locomotor executive circuits of the spinal cord, that are directly targeted by RS pathway identified throughout the work. This will touch upon the cooperative role of the brainstem and spinal cord in elaborating behaviors, and will be instrumental information to remedy unbalanced hypo-/hyper-excitable states of the network in pathological or post-traumatic conditions.