Regularizing firing patterns of rat subthalamic neurons ameliorates parkinsonian motor deficits
| Autor: | Xiao-Yang Zhang, Jian-Jun Wang, Guang-Ying Li, Hong-Zhao Li, Chang-Zheng Zhang, Qian-Xing Zhuang, Kang Xi, Jing-Ning Zhu, Bin Li |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Journal of Clinical Investigation. 128:5413-5427 |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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