THE FUNCTIONS OF MOUSE SPINAL V3 INTERNEURONS IN LOCOMOTION

Abstract

V3 interneurons (INs) are a major group of glutamatergic commissural neurons in the mouse spinal cord. They directly innervate motor neurons (MNs) as well as other ventral INs. Although it has been shown that V3 INs are crucial in generating stable and robust rhythmic locomotor activities, the mechanisms underlying their functions are still unclear. In my current study, I delete the expression of Vesicular Glutamate Transporter 2 (vGluT2) in V3 INs in Sim1Cre/+;vGluT2 flox/flox (V3OFF) mice, and systematically examine their locomotor behaviours, including their gaits at various treadmill speeds, as well as their kinematics and muscle activities in different locomotor tasks. Firstly, I identify a subset of V3 INs that might regulate the coordination of fore- and hind-limbs for trotting movements. Secondly, I find that V3 INs have task-dependent functional roles in regulating proximal or distal joints. They facilitate hip joint movements in all locomotor tasks, while only regulating distal joint activities in weight-bearing behaviours. In addition, using optogenetic tools, I also investigate the functions of V3 INs in fictive locomotion of the neonatal spinal cord. In combination with computational modelling studies, we provide convincing evidence that V3 INs contribute to the synchronization of the left-right locomotor outputs by providing mutual excitation between the extensor centres in the left and right central pattern generator (CPG) circuits. Thus, my study reveals that spinal V3 INs potentially have multiple functional subpopulations that play various specific and critical roles in regulating locomotor behaviours under different conditions.