Striatal direct pathway neurons play leading roles in accelerating rotarod motor skill learning
Bo Liang,
Lifeng Zhang,
Yan Zhang,
Craig T. Werner,
Nicholas J. Beacher,
Alex J. Denman,
Yun Li,
Rong Chen,
Charles R. Gerfen,
Giovanni Barbera,
Da-Ting Lin
Affiliations
Bo Liang
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA; School of Electrical Engineering & Computer Science, College of Engineering & Mines, University of North Dakota, Grand Forks, ND 58202, USA
Lifeng Zhang
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA
Yan Zhang
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA
Craig T. Werner
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA
Nicholas J. Beacher
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA
Alex J. Denman
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA
Yun Li
Department of Zoology and Physiology, University of Wyoming, 1000 E University Avenue, Laramie, WY 82071, USA
Rong Chen
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 100 N Greene St, Baltimore, MD 21201, USA
Charles R. Gerfen
Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 49, Room 5A60, Bethesda, MD 20814, USA
Giovanni Barbera
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA; Corresponding author
Da-Ting Lin
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA; Corresponding author
Summary: Dorsal striatum is important for movement control and motor skill learning. However, it remains unclear how the spatially and temporally distributed striatal medium spiny neuron (MSN) activity in the direct and indirect pathways (D1 and D2 MSNs, respectively) encodes motor skill learning. Combining miniature fluorescence microscopy with an accelerating rotarod procedure, we identified two distinct MSN subpopulations involved in accelerating rotarod learning. In both D1 and D2 MSNs, we observed neurons that displayed activity tuned to acceleration during early stages of trials, as well as movement speed during late stages of trials. We found a distinct evolution trajectory for early-stage neurons during motor skill learning, with the evolution of D1 MSNs correlating strongly with performance improvement. Importantly, optogenetic inhibition of the early-stage neural activity in D1 MSNs, but not D2 MSNs, impaired accelerating rotarod learning. Together, this study provides insight into striatal D1 and D2 MSNs encoding motor skill learning.
