Periodic Reporting for period 3 - Descent (Control of Action Diversification by Descending Motor CircuitsControl of action diversification by descending motor circuits)
Reporting period: 2019-09-01 to 2021-02-28
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.
Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far
We have made significant progress on understanding neurons in the caudal brainstem, a region in which neurons with projections to both lumbar and cervical spinal levels reside. We found that medullary neuronal populations subdivide into classes with different behavioral functions (Capelli et al., Nature 2017). A small subregion within the medulla, called LPGi, harbors excitatory neurons that are absolutely essential for high-speed locomotion (Capelli et al., Nature 2017) and activation of intermingled inhibitory neurons leads to behavioral arrest. Descending brainstem neurons communicate with neurons in the spinal cord, including long descending spinal projection neurons, which we found to be essential to regulate several full-body movement parameters (Ruder et al., Neuron 2016). We have also addressed the role of motor cortex in a virtual reality task navigation task, introducing unexpected sensory perturbations (Heindorf et al., Neuron 2018). We found that cortical neurons show distinct activity patterns when mice carry out the same movement either spontaneously or upon introduced unexpected sensory perturbation, but the motor cortex is only essential for performance of the latter. Most recently, we have studied the source and mechanism of how proprioceptive afferents influence functional recovery after spinal cord injury (Takeoka and Arber, Cell Reports, 2019). The work on neuronal circuits controlling diverse movement has also been reviewed by us in three recent papers published (Arber and Costa, Science 2018; Pinto et al., Neuron 2018; Ruder and Arber, Annual Reviews Neuroscience 2019).
Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)
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.