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08 25, 2023;9 (34): eadg3038.

Reduced thalamic excitation to motor cortical pyramidal tract neurons in parkinsonism.

Liqiang Chen, Samuel Daniels, Rachel Dvorak, Hong-Yuan Chu
Author Information
  1. Liqiang Chen: Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503 USA. ORCID
  2. Samuel Daniels: Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503 USA. ORCID
  3. Rachel Dvorak: Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503 USA. ORCID
  4. Hong-Yuan Chu: Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503 USA. ORCID
PMID: 37611096 DOI: 10.1126/sciadv.adg3038

Abstract

Degeneration of midbrain dopaminergic (DA) neurons alters the connectivity and functionality of the basal ganglia-thalamocortical circuits in Parkinson's disease (PD). Particularly, the aberrant outputs of the primary motor cortex (M1) contribute to parkinsonian motor deficits. However, cortical adaptations at cellular and synaptic levels in parkinsonism remain poorly understood. Using multidisciplinary approaches, we found that DA degeneration induces cell subtype- and input-specific reduction of thalamic excitation to M1 pyramidal tract (PT) neurons. At molecular level, we identified that -methyl-d-aspartate (NMDA) receptors play a key role in mediating the reduced thalamocortical excitation to PT neurons. At circuit level, we showed that the reduced thalamocortical transmission in parkinsonian mice can be rescued by chemogenetically suppressing basal ganglia outputs. Together, our data suggest that cell subtype- and synapse-specific adaptations in M1 contribute to altered cortical outputs in parkinsonism and are important aspects of PD pathophysiology.

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Grants

  1. R01 NS121371/NINDS NIH HHS

MeSH Term

Animals
Mice
Pyramidal Tracts
Motor Neurons
Parkinsonian Disorders
Parkinson Disease
Basal Ganglia
Receptors, N-Methyl-D-Aspartate

Chemicals

Receptors, N-Methyl-D-Aspartate
Journal Article
Article has an altmetric score of 79

Word Cloud

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