Reduced thalamic excitation to motor cortical pyramidal tract neurons in parkinsonism

• DOI: 10.1126/sciadv.adg3038
• Publication Date: 2023-08-23T17:58:33Z
• Authors: Liqiang Chen; Samuel Daniels; Rachel Dvorak; Hong-Yuan Chu
• Keywords: Pyramidal tracts

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