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Regularizing firing patterns of rat subthalamic neurons ameliorates parkinsonian motor deficits
- Source :
- Journal of Clinical Investigation. 128:5413-5427
- Publication Year :
- 2018
- Publisher :
- American Society for Clinical Investigation, 2018.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
Deep brain stimulation
Parkinson's disease
Deep Brain Stimulation
medicine.medical_treatment
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Histamine H2 receptor
Subthalamic Nucleus
Basal ganglia
Animals
Medicine
Parkinson Disease, Secondary
Neurons
business.industry
Motor Cortex
Histaminergic
Motor control
General Medicine
medicine.disease
Rats
nervous system diseases
Subthalamic nucleus
surgical procedures, operative
030104 developmental biology
nervous system
chemistry
Commentary
Beta Rhythm
business
therapeutics
Neuroscience
030217 neurology & neurosurgery
Histamine
Subjects
Details
- ISSN :
- 15588238 and 00219738
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....4896f55d86121e01e49ab31b5de3f16b