Reduced Thalamic Excitation to Motor Cortical Pyramidal Tract Neurons in Parkinsonism

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 parkinsonian state 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 NMDA receptors play a key role in mediating the reduced thalamocortical excitation to PT neurons. At circuit level, we showed that the decreased thalamocortical transmission in parkinsonian mice can be rescued by chemogenetically suppressing basal ganglia outputs. Together, our data suggest that cellular and synaptic adaptions in M1 neuron subtypes contribute to the reduced cortical outputs in parkinsonian state and are important aspects of PD pathophysiology. Teaser Specific motor cortical plasticity contributes to Parkinson’s pathophysiology in mouse models of the disease.