机构:[1]Department of Neurobiology, Center for Neuroscience and The Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA.[2]Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.[3]Department of Neuroscience, Columbia University Medical Center, New York, NY.[4]Zuckerman Institute, Columbia University, New York, NY, USA.[5]Department of Neurology, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, China.神经科系统神经内科首都医科大学宣武医院[6]Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Although the basal ganglia (BG) plays a central role in the motor symptoms of Parkinson's disease, few studies have investigated the influence of parkinsonism on movement-related activity in the BG. Here, we studied the perimovement activity of neurons in globus pallidus internus (GPi) of non-human primates during performance of a choice reaction time reaching task before and after the induction of parkinsonism by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal responses, including increases or decreases in firing rate, were equally common in the parkinsonian brain as seen prior to MPTP and the distribution of different response types was largely unchanged. The slowing of behavioral reaction times and movement durations following the induction of parkinsonism was accompanied by a prolongation of the time interval between neuronal response onset and movement initiation. Neuronal responses were also reduced in magnitude and prolonged in duration after the induction of parkinsonism. Importantly, those two effects were more pronounced among decrease-type responses, and they persisted after controlling for MPTP-induced changes in the between-trial variability in response timing. Following MPTP the trial-to-trial timing of neuronal responses also became uncoupled from the time of movement onset and more variable in general. Overall, the effects of MPTP on temporal features of GPi responses were related to the severity of parkinsonian motor impairments whereas changes in response magnitude and duration did not reflect symptom severity consistently. These findings point to a previously underappreciated potential role for abnormalities in the timing of GPi task-related activity in the generation of parkinsonian motor signs.
基金:
National Institute of Neurological Disorders and Stroke at the
National Institutes of Health (Grant Numbers R01 NS117058-01 and R01 NS070865-01A1 to
RST; www.ninds.nih.gov/). Additionally, this research was funded in part by Aligning Science Across Parkinson’s (ASAP-020519);Parkinson’s Research (MJFF).
语种:
外文
PubmedID:
第一作者:
第一作者机构:[1]Department of Neurobiology, Center for Neuroscience and The Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA.[2]Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
通讯作者:
通讯机构:[1]Department of Neurobiology, Center for Neuroscience and The Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA.[2]Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
推荐引用方式(GB/T 7714):
Kase Daisuke,Zimnik Andrew J,Han Yan,et al.Movement-related activity in the internal globus pallidus of the parkinsonian macaque[J].Biorxiv : The Preprint Server For Biology.2025,doi:10.1101/2024.08.29.610310.
APA:
Kase Daisuke,Zimnik Andrew J,Han Yan,Harsch Devin R,Bacha Sarah...&Turner Robert S.(2025).Movement-related activity in the internal globus pallidus of the parkinsonian macaque.Biorxiv : The Preprint Server For Biology,,
MLA:
Kase Daisuke,et al."Movement-related activity in the internal globus pallidus of the parkinsonian macaque".Biorxiv : The Preprint Server For Biology .(2025)