Jared Cregg

Assistant professor, Kiehn Lab

Title

Basal ganglia-spinal cord pathway that commands locomotor gait asymmetries

Abstract

Locomotion is a natural behavior that can be parsed into distinct features, including speed and stop. While the circuits responsible for such features of locomotion have been described in some detail, how descending circuits direct locomotor movements to the left or right side has remained unclear. In the first part of my seminar, I will present our recent discovery that Chx10-lineage reticulospinal neurons are required for turning gait asymmetries and represent the primary descending command line for turning in mammals (Cregg et al, Nat Neurosci, 2020).  

The primacy of turning is exemplified in Parkinsonian patients, which exhibit exacerbated turning deficits often accompanied by falls. In the second part of my seminar, I will present our latest work aimed at understanding turning gait deficits in Parkinson’s disease (PD), a disorder of the basal ganglia. Using deep brainstem Ca²⁺ recording, intersectional viral tracing, and optogenetics in freely moving mice, we uncovered the principal basal ganglia-spinal cord pathway for turning gait asymmetries in mammals: striatal projection neurons à substantia nigra pars reticulata à pontine nucleus oralis à Chx10 neurons à spinal locomotor networks. We then took advantage of this pathway information to ameliorate turning deficits in mice with striatal dopamine depletion. Our results reveal the circuit logic underlying a critical motor program, from action commitment in the basal ganglia to execution by spinal locomotor networks, and provide a circuit-level understanding of turning gait deficits in PD.