Characterization of spinal learning in a repetitive yet skilled locomotor task
Animals adjust movement throughout their life to adapt to a changing environment and to learn new motor skills. The underlying mechanisms have been studied for decades, almost exclusively as a function of the brain. Interestingly,...
Animals adjust movement throughout their life to adapt to a changing environment and to learn new motor skills. The underlying mechanisms have been studied for decades, almost exclusively as a function of the brain. Interestingly, however, the spinal cord adapts and learns motor sequences without the brain, using only spinal sensory feedback. Therefore, the spinal cord must contain adequate neuronal circuitry for motor learning. This project aims to characterize brain-independent mechanisms of learning that take place within the spinal cord. With a complete thoracic transection, I will functionally isolate the lumbar spinal cord from the brain and enable hindlimb locomotion on a motorized treadmill with pharmacological stimulation. Using a skilled yet repetitive locomotor paradigm, I will identify cell-types indispensable for obstacle learning through circuit manipulation. Our preliminary data indicate that mice learn to avoid obstacles and improve their performance over weeks. We will test the integrity of this performance upon specific and acute inhibition of a selected neuronal population during the behavioral task. Furthermore, using in-vivo awake eletrophysiological recordings, I will characterize circuit dynamics that underlie motor learning capacity attributed to the spinal cord while mice perform the obstacle task. This project maximizes the synergies of the host lab’s expertise, i.e., kinematic analysis, circuit dissection, and the use of high-density Neuropixel probes, and my expertise in electrophysiological recordings in mouse spinal cord. In addition to implementing an innovative system of multichannel recordings of spinal circuits in behaving mice, knowledge gained from this project will enable linking cell-type specific activity profiles in the spinal cord to a motor learning behaviour for the first time. This link is an essential yet currently missing piece to understand how the spinal cord contributes to the acquisition of a new motor repertoire.ver más
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