Summary: Abnormal activity involving the globus pallidus may be responsible for movement dysfunction in Parkinson’s disease, a new study reports.
Source: Northwestern University.
The prevailing consensus was that excessive patterning of the subthalamic nucleus (STN), a component of the basal ganglia, by the cerebral cortex was linked to the symptomatic expression of Parkinson’s disease, including muscle rigidity and slowness of movement. NeuroscienceNews.com image is in the public domain.
Source: Marla Paul – Northwestern University
•Cortico-STN synaptic transmission is reduced by 50%–75% in PD mice
•Increased striato-pallidal transmission triggers cortico-STN input loss
•Cortico-STN input loss in PD mice is NMDAR dependent
•Reduction of STN plasticity is therapeutic in PD mice
The motor symptoms of Parkinson’s disease (PD) are linked to abnormally correlated and coherent activity in the cortex and subthalamic nucleus (STN). However, in parkinsonian mice we found that cortico-STN transmission strength had diminished by 50%–75% through loss of axo-dendritic and axo-spinous synapses, was incapable of long-term potentiation, and less effectively patterned STN activity. Optogenetic, chemogenetic, genetic, and pharmacological interrogation suggested that downregulation of cortico-STN transmission in PD mice was triggered by increased striato-pallidal transmission, leading to disinhibition of the STN and increased activation of STN NMDA receptors. Knockdown of STN NMDA receptors, which also suppresses proliferation of GABAergic pallido-STN inputs in PD mice, reduced loss of cortico-STN transmission and patterning and improved motor function. Together, the data suggest that loss of dopamine triggers a maladaptive shift in the balance of synaptic excitation and inhibition in the STN, which contributes to parkinsonian activity and motor dysfunction.