Unraveling the role of spinal GABApre neurons in presynaptic modulation during locomotion

ongoing

"Presynaptic modulation is a cornerstone of neural function, shaping everything from basic motor control to sensory processing and motor learning. It is a powerful mechanism that allow the fine tuning of a neuron selected target through an axonal modulation. In the spinal cord, this potent modulation is mediated by ""GABApre"" neurons. However, although widely studied ex-vivo, their function during naturalistic behaviors remains poorly understood due to technical challenges limiting in vivo access to spinal neurons. By leveraging advanced methodologies, such as in vivo electrophysiological recordings with Neuropixel probes during naturalistic locomotion, this project aims to uncover mechanisms that have so far remained elusive. Combining genetic manipulation, viral targeting, and high-resolution 3D kinematic analysis, this project will investigate the activity of GABApre neurons and their impact on motoneuron dynamics and locomotor performance across movement phases and muscle recruitment. Additionally, we will explore the recently observed dual effect of GABApre neurons and determine whether they consist of distinct subpopulations and whether they exhibit distinct context-dependent functions. By examining GABApre function during natural locomotion, this work will bridge the gap between previous non-physiological studies and the real-world relevance of presynaptic modulation, offering new insights into sensorimotor integration and adaptive motor behavior. While fundamental, this project’s discoveries will provide a crucial foundation for the design of innovative therapeutic approaches. "