Maladaptive Downregulation of Autonomous Subthalamic Nucleus Activity following the Loss of Midbrain Dopamine Neurons.

ABSTRACT: Abnormal subthalamic nucleus (STN) activity is linked to impaired movement in Parkinson's disease (PD). The autonomous firing of STN neurons, which contributes to their tonic excitation of the extrastriatal basal ganglia and shapes their integration of synaptic input, is downregulated in PD models. Using electrophysiological, chemogenetic, genetic, and optical approaches, we find that chemogenetic activation of indirect pathway striatopallidal neurons downregulates intrinsic STN activity in normal mice but this effect is occluded in Parkinsonian mice. Loss of autonomous spiking in PD mice is prevented by STN N-methyl-D-aspartate receptor (NMDAR) knockdown and reversed by reactive oxygen species breakdown or K_ATP channel inhibition. Chemogenetic activation of hM3D(Gq) in STN neur

SUBMITTER: McIver EL 

PROVIDER: S-EPMC6699776 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature