Regularizing firing patterns of rat subthalamic neurons ameliorates parkinsonian motor deficits

The Journal of Clinical Investigation
Qian-Xing ZhuangJing-Ning Zhu

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...Continue Reading

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Citations

Oct 30, 2018·The Journal of Clinical Investigation·Timothy C Whalen, Aryn H Gittis
May 21, 2019·Frontiers in Cellular Neuroscience·Guang-Ying LiJing-Ning Zhu
Dec 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xiao-Yang ZhangJing-Ning Zhu
May 28, 2021·SLAS Discovery·Kosuke NakashimaHideki Matsui

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Methods Mentioned

BETA
PCR
ELISA
dissectors
Assay

Key Resources (RRID) Mentioned

AB_94698
AB_1640532
AB_177540
AB_572245
AB_477569
AB_2230568
AB_2277328
AB_2121375
AB_2119026
AB_2039900

Software Mentioned

- ASW
Agilent ChemStation
Spike
Integromics
Time StatMiner
Image Pro Plus
Photoshop
FV10
NeuroExplorer
Real

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