Emergence of Task-Related Motor Cortical Dysfunction in Mice with Progressive Parkinsonism
- 1Georgetown University
Abstract
The primary motor cortex (M1) exhibits substantial changes in Parkinsons disease (PD). However, the temporal relationship between midbrain dopamine (DA) neurodegeneration, M1 circuit dysfunction, and motor symptoms remains poorly understood. Using the MitoPark mice, we investigated the time course of M1 cellular dysfunction during progressive DA loss. MitoPark mice developed gradually impaired skilled movements at a moderate motor stage of Parkinsonism. The motor deficits were associated with reduced cellular activity, impaired neuronal coactivation, and decreased proportion of responsive M1 pyramidal neurons. Moreover, the corticospinal (CSp), but not the intratelencephalic (IT), neurons showed a selective reduction in cellular activity during reaches. At the population level, M1 pyramidal neurons included heterogeneous functional clusters in relation to skilled movements and their stability in longitudinal encoding of movement degraded substantially in MitoPark mice. Together, these results delineate the emergence of M1 circuit pathophysiology at cellular and neural population levels during progressive Parkinsonism.
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BibTeX
@misc{chehade2026emergence,
title = {{Emergence of Task-Related Motor Cortical Dysfunction in Mice with Progressive Parkinsonism}},
author = {H. D. Chehade and D. Berezhnoi and S. Somavarapu and Z. Wang and J. Jiang and L. Chen and B. B. Risk and T. Wichmann and H.-Y. Chu},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.29.728524},
url = {https://www.biorxiv.org/content/10.64898/2026.05.29.728524v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Emergence of Task-Related Motor Cortical Dysfunction in Mice with Progressive Parkinsonism
AU - H. D. Chehade
AU - D. Berezhnoi
AU - S. Somavarapu
AU - Z. Wang
AU - J. Jiang
AU - L. Chen
AU - B. B. Risk
AU - T. Wichmann
AU - H.-Y. Chu
PY - 2026
DA - 2026/05/29
PB - bioRxiv
DO - 10.64898/2026.05.29.728524
UR - https://www.biorxiv.org/content/10.64898/2026.05.29.728524v2
AB - The primary motor cortex (M1) exhibits substantial changes in Parkinsons disease (PD). However, the temporal relationship between midbrain dopamine (DA) neurodegeneration, M1 circuit dysfunction, and motor symptoms remains poorly understood. Using the MitoPark mice, we investigated the time course of M1 cellular dysfunction during progressive DA loss. MitoPark mice developed gradually impaired skilled movements at a moderate motor stage of Parkinsonism. The motor deficits were associated with reduced cellular activity, impaired neuronal coactivation, and decreased proportion of responsive M1 pyramidal neurons. Moreover, the corticospinal (CSp), but not the intratelencephalic (IT), neurons showed a selective reduction in cellular activity during reaches. At the population level, M1 pyramidal neurons included heterogeneous functional clusters in relation to skilled movements and their stability in longitudinal encoding of movement degraded substantially in MitoPark mice. Together, these results delineate the emergence of M1 circuit pathophysiology at cellular and neural population levels during progressive Parkinsonism.
ER -