Delineating excitatory V3 interneuron diversity in the mouse spinal cord

Abstract

Mammals possess the remarkable ability to manoeuver the physical world with precise, coordinated, and autonomous control. Interneuron networks in the spinal cord simultaneously integrate and process supraspinal and sensory information while generating basic rhythmic and patterned motor commands. Thus, sensorimotor spinal interneuron circuits ensure the successful execution of goal- and context-specific movement. Utilizing the mouse model system, my Ph.D. work has focused on understanding: 1) the spinal interneuron diversity underlying functionally distinct circuit organizations; and then 2) how that diversity emerges during early embryogenesis. With a focus on excitatory V3 and V2a cardinal interneuron populations in the spinal cord, I first reveal that these two excitatory spinal interneurons topographically cluster into task-specific recruitment modules, which may functionally compensate in the absence of one another. Thus, molecularly and anatomically distinct interneuron subpopulations may be functionally organized based on their behaviour-specific recruitments. Second, I investigate the early embryonic mechanisms guiding the subpopulation diversification of V3 interneurons. I reveal that V3 interneuron subpopulations diversify across hierarchical temporal and spatial developmental pathways. Specifically, differential neurogenesis timing separates V3 INs into either early-born or late-born temporal subclasses leading to distinct transcription factor expression patterns and neuronal migration trajectories. Within each temporal subclass, spatial controls then further delineate V3 INs into molecularly, anatomically, morphologically, and electrophysiologically distinct subpopulations. Taken together, my Ph.D. work has revealed key developmental and functional logic underlying the diversification of excitatory interneurons within the mammalian spinal cord.