| First Author | Chu HY | Year | 2017 |
| Journal | Neuron | Volume | 95 |
| Issue | 6 | Pages | 1306-1318.e5 |
| PubMed ID | 28910619 | Mgi Jnum | J:256047 |
| Mgi Id | MGI:6114309 | Doi | 10.1016/j.neuron.2017.08.038 |
| Citation | Chu HY, et al. (2017) Loss of Hyperdirect Pathway Cortico-Subthalamic Inputs Following Degeneration of Midbrain Dopamine Neurons. Neuron 95(6):1306-1318.e5 |
| abstractText | 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. |
