Altered Thalamocortical Signaling in a Mouse Model of Parkinson's Disease

Abstract

Activation of the primary motor cortex (M1) is important for the execution of skilled movements and motor learning, and its dysfunction contributes to the pathophysiology of Parkinsons disease (PD). A well accepted idea in PD research, albeit not tested experimentally, is that loss of midbrain dopamine leads to decreased activation of M1 by the motor thalamus (Mthal). Here, we report that midbrain dopamine loss reduced Mthal input in a laminar- and cell type-specific fashion and induced laminar-specific changes in intracortical synaptic transmission. As a result, M1 activation by Mthal was decreased, but M1 output was increased. Our results demonstrate that loss of midbrain dopaminergic neurons alters thalamocortical activation of M1, and provide novel insights into circuit mechanisms for motor cortex dysfunction in a mouse model of PD.