Abstract
The subthalamic nucleus (STN) is traditionally thought to restrict movement. Lesion or prolonged STN inhibition increases movement vigor and propensity, while optogenetic excitation has opposing effects. However, STN neurons often exhibit movement-related increases in firing. To address this paradox, STN activity was recorded and manipulated in head-fixed mice at rest and during self-initiated and self-paced treadmill locomotion. We found that (1) most STN neurons (type 1) exhibit locomotion-dependent increases in activity, with half firing preferentially during the propulsive phase of the contralateral locomotor cycle; (2) a minority of STN neurons exhibit dips in activity or are uncorrelated with movement; (3) brief optogenetic inhibition of the lateral STN (where type 1 neurons are concentrated) slows and prematurely terminates locomotion; and (4) in Q175 Huntington's disease mice, abnormally brief, low-velocity locomotion is associated with type 1 hypoactivity. Together, these data argue that movement-related increases in STN activity contribute to optimal locomotor performance.
| Original language | English (US) |
|---|---|
| Article number | 114495 |
| Journal | Cell reports |
| Volume | 43 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 27 2024 |
Funding
This work was funded by grants from CHDI Foundation (A-5071), Aligning Science Across Parkinson's (ASAP-020600), and NIH-NINDS (R01 NS041280 and R01 NS121174). The authors thank Sasha Ulrich, Danielle Rae Schowalter, and Marisha Alicea for maintenance of mouse colonies and Drs. Vahri Beaumont, Roger Cachope, and Ignacio Munoz-Sanjuan for helpful discussions and advice throughout the execution of this study. Conceptualization: J.W.C. and M.D.B.; methodology: J.W.C. J.C.M. J.F.A. and M.D.B.; validation: J.W.C. J.C.M. J.F.A. and M.D.B.; formal analysis: J.W.C. J.C.M. J.F.A. and M.D.B.; investigation: J.W.C. D.W. and S.K.; data curation: J.W.C. and M.D.B.; writing \u2013 original draft, J.W.C. and M.D.B.; writing \u2013 editing, J.W.C. J.C.M. J.F.A. D.W. S.K. and M.D.B.; visualization, J.W.C. J.C.M. J.F.A. and M.D.B.; supervision, J.W.C. and M.D.B.; project administration, J.W.C. and M.D.B.; funding acquisition, M.D.B. The authors declare no competing interests. This work was funded by grants from CHDI Foundation ( A-5071 ), Aligning Science Across Parkinson's ( ASAP-020600 ), and NIH-NINDS ( R01 NS041280 and R01 NS121174 ). The authors thank Sasha Ulrich, Danielle Rae Schowalter, and Marisha Alicea for maintenance of mouse colonies and Drs. Vahri Beaumont, Roger Cachope, and Ignacio Munoz-Sanjuan for helpful discussions and advice throughout the execution of this study.
Keywords
- CP: Neuroscience
- Huntington's disease
- Parkinson's disease
- action execution
- basal ganglia
- deep brain stimulation
- gait
- hyperdirect pathway
- indirect pathway
- motor control
- neuromodulation
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology