HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress. Elife 2018 Jan 02;7
Date
12/20/2017Pubmed ID
29256865Pubmed Central ID
PMC5749952DOI
10.7554/eLife.32420Scopus ID
2-s2.0-85044160251 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naïve mice, whereas VTA HCN2 overexpression largely prevented CMS-induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors.
Author List
Zhong P, Vickstrom CR, Liu X, Hu Y, Yu L, Yu HG, Liu QSAuthor
Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Action PotentialsAnimals
Depression
Dopaminergic Neurons
Gene Expression
Gene Knockdown Techniques
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Mice
Potassium Channels
Stress, Physiological
Ventral Tegmental Area
