| First Author | Zhong P | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 29256865 | Mgi Jnum | J:256759 |
| Mgi Id | MGI:6112520 | Doi | 10.7554/eLife.32420 |
| Citation | Zhong P, et al. (2018) HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress. Elife 7:e32420 |
| abstractText | 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-naive 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. |
