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HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress.
- Source :
-
eLife . Dec2017, p1-27. 27p. - Publication Year :
- 2017
-
Abstract
- 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-naıve 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2050084X
- Database :
- Academic Search Index
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- 134313527
- Full Text :
- https://doi.org/10.7554/eLife.32420