Periodic Reporting for period 4 - Descent (Control of Action Diversification by Descending Motor CircuitsControl of action diversification by descending motor circuits)
Reporting period: 2021-03-01 to 2022-06-30
Movement is the behavioral output of the nervous system. Animals carry out an enormous repertoire of distinct actions, spanning from seemingly simple repetitive tasks like walking to much more complex movements such as forelimb manipulation tasks. An important question is how neuronal circuits are organized and function to choose, maintain, adjust and terminate these many distinct motor behaviors. The goal of this research project is to unravel the circuit blueprint of mouse descending motor pathways at a fine-scale level and to probe the intersection between revealed circuit organization and their behavioral function at many levels. Our project elucidates the circuit organization and function of the descending motor output system and thereby uncovers principles of how the nervous system generates diverse actions.
Our project has made significant progress in understanding the organization and function of neurons in the brainstem, a structure just upstream of the spinal cord. The brainstem is instrumental in sending commands to the spinal cord needed to initiate, maintain or change body movements. The focus of this work was mostly on two fundamentally distinct forms of body movement, namely full body movements including locomotion on the one hand, and skilled forelimb movements on the other hand. We found that there are dedicated networks of neurons in the caudal brainstem regulating the execution of these distinct behaviors. Most notably, the specific neurons we identified are central to the regulation of these behaviors, and are organized into distinct and highly specific circuits. These findings provide essential entry points to program movement in specific ways in patients with disabilities in upper motor centers such as Parkinson’s disease or stroke. By using this knowledge, one can anticipate that personalized medicine for specific forms of movement can be developed in the future. The findings have found broad recognition and the body of work including the results from this ERC grant have recently been recognized with the prestigious Brain Prize.
Through gained knowledge, predicted interference with and changing of animal behavior through targeted interventions should be possible in the longer run. Our studies should therefore also be able to contribute to and guide future studies on reestablishing motor function in neurodegenerative disorders such as Parkinson’s disease, or after spinal cord injury. Revealing principles of motor circuit organization and function will also contribute to our understanding of how circuits work outside the motor system and in evolutionarily higher species than mice. We suspect that the insight emerging through our work will be widely applicable.