English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Burst firing has been reported as a pathological activity of subthalamic nucleus (STN) neurons in Parkinson's disease. However, the origin of bursts and their causal link with motor deficits remain unknown. Here we tested the hypothesis that dopamine D5 receptors (D5Rs), characterized by a high constitutive activity, may contribute to the emergence of burst firing in STN. We tested whether inhibiting D5R constitutive activity depresses burst firing and alleviates motor impairments in the 6-OHDA rat model of Parkinson's disease. Intrasubthalamic microinjections of either an inverse agonist of D5Rs, flupenthixol, or a D2R antagonist, raclopride, were applied. Behavioral experiments, in vivo and in vitro electrophysiological recordings, and ex vivo functional neuroanatomy studies were performed. Using [(5)S]GTPγ binding autoradiography, we show that application of flupenthixol inhibits D5R constitutive activity within the STN. Furthermore, flupenthixol reduced evoked burst in brain slices and converted pathological burst firing into physiological tonic, single-spike firing in 6-OHDA rats in vivo. This later action was mimicked by calciseptine, a Cav1 channel blocker. Moreover, the same treatment dramatically attenuated motor impairment in this model and normalized metabolic hyperactivity in both STN and substantia nigra pars reticulata, the main output structure of basal ganglia in rats. In contrast, raclopride as well as saline did not reverse burst firing and motor deficits, confirming the selective action of flupenthixol on D5Rs. These results are the first to demonstrate that subthalamic D5Rs are involved in the pathophysiology of Parkinson's disease and that administering an inverse agonist of these receptors may lessen motor symptoms.

the journal of neuroscience/the journal of neuroscience

Inhibiting Subthalamic D<sub>5</sub>Receptor Constitutive Activity Alleviates Abnormal Electrical Activity and Reverses Motor Impairment in a Rat Model of Parkinson's Disease

Inhibiting Subthalamic D5Receptor Constitutive Activity Alleviates Abnormal Electrical Activity and Reverses Motor Impairment in a Rat Model of Parkinson's Disease

Inhibiting Subthalamic D₅Receptor Constitutive Activity Alleviates Abnormal Electrical Activity and Reverses Motor Impairment in a Rat Model of Parkinson's Disease