Searching across hundreds of databases
The subthalamic nucleus (STN) is an effective therapeutic target for deep brain stimulation (DBS) for Parkinson's disease (PD), and histamine levels are elevated in the basal ganglia in PD patients. However, the effect of endogenous histaminergic modulation on STN neuronal activities and the neuronal mechanism underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns are more crucial than firing rates for motor control. Histamine excited STN neurons, but paradoxically ameliorated parkinsonian motor deficits, which we attributed to regularizing firing patterns of STN neurons via the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the STN and regularized STN neuronal firing patterns under parkinsonian conditions. HCN2 contributed to the DBS-induced regularization of neuronal firing patterns, suppression of excessive β oscillations, and alleviation of motor deficits in PD. The results reveal an indispensable role for regularizing STN neuronal firing patterns in amelioration of parkinsonian motor dysfunction and a functional compensation for histamine in parkinsonian basal ganglia circuitry. The findings provide insights into mechanisms of STN-DBS as well as potential therapeutic targets and STN-DBS strategies for PD.
Pubmed ID: 30226827 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This unknown targets HCN2 Channel
View all literature mentionsThis unknown targets HCN3 Channel
View all literature mentionsThis unknown targets HCN4 Channel
View all literature mentionsThis unknown targets HCN1 Channel
View all literature mentionsThis polyclonal targets Histamine H4 Receptor
View all literature mentionsThis polyclonal targets Histamine Receptor H2
View all literature mentionsThis polyclonal targets HRH1
View all literature mentionsThis polyclonal targets Histamine Receptor H1 (C Term)
View all literature mentionsThis monoclonal targets Tyrosine Hydroxylase
View all literature mentionsThis polyclonal targets Histamine
View all literature mentionsThis polyclonal targets Histamine
View all literature mentionsThis polyclonal targets GAD67 antibody
View all literature mentionsThis monoclonal targets Glutamate
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
