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HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress.
Zhong, Peng; Vickstrom, Casey R; Liu, Xiaojie; Hu, Ying; Yu, Laikang; Yu, Han-Gang; Liu, Qing-Song.
Afiliación
  • Zhong P; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, United States.
  • Vickstrom CR; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, United States.
  • Liu X; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, United States.
  • Hu Y; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, United States.
  • Yu L; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, United States.
  • Yu HG; Department of Physiology and Pharmacology, West Virginia University, Morgantown, United States.
  • Liu QS; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, United States.
Elife ; 72018 01 02.
Article en En | MEDLINE | ID: mdl-29256865
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Fisiológico / Canales de Potasio / Área Tegmental Ventral / Depresión / Neuronas Dopaminérgicas / Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización Límite: Animals Idioma: En Revista: Elife Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Fisiológico / Canales de Potasio / Área Tegmental Ventral / Depresión / Neuronas Dopaminérgicas / Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización Límite: Animals Idioma: En Revista: Elife Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido