Dataset Information

?1- and ?3-Adrenergic Receptor-Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice.

ABSTRACT: BACKGROUND:Homeostatic plasticity in mesolimbic dopamine (DA) neurons plays an essential role in mediating resilience to social stress. Recent evidence implicates an association between stress resilience and projections from the locus coeruleus (LC) to the ventral tegmental area (VTA) (LC?VTA) DA system. However, the precise circuitry and molecular mechanisms of the homeostatic plasticity in mesolimbic DA neurons mediated by the LC?VTA circuitry, and its role in conferring resilience to social defeat stress, have not been described. METHODS:In a well-established chronic social defeat stress model of depression, using projection-specific electrophysiological recordings and optogenetic, pharmacological, and molecular profiling techniques, we investigated the functional role and molecular basis of an LC?VTA circuit in conferring resilience to social defeat stress. RESULTS:We found that LC neurons projecting to the VTA exhibit enhanced firing activity in resilient, but not susceptible, mice. Optogenetically mimicking this firing adaptation in susceptible mice reverses their depression-related behaviors, and induces reversal of cellular hyperactivity and homeostatic plasticity in VTA DA neurons projecting to the nucleus accumbens. Circuit-specific molecular profiling studies reveal that ?1- and ?3-adrenergic receptors are highly expressed in VTA?nucleus accumbens DA neurons. Pharmacologically activating these receptors induces similar proresilient effects at the ion channel and cellular and behavioral levels, whereas antagonizing these receptors blocks the proresilient effect of optogenetic activation of LC?VTA circuit neurons in susceptible mice. CONCLUSIONS:These findings reveal a key role of the LC?VTA circuit in mediating homeostatic plasticity in stress resilience and reveal ?1- and ?3-adrenergic receptors as new molecular targets for therapeutically promoting resilience.

SUBMITTER: Zhang H

PROVIDER: S-EPMC6800029 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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α1- and β3-Adrenergic Receptor-Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice.

Zhang Hongxing H Chaudhury Dipesh D Nectow Alexander R AR Friedman Allyson K AK Zhang Song S Juarez Barbara B Liu He H Pfau Madeline L ML Aleyasin Hossein H Jiang Cheng C Crumiller Marshall M Calipari Erin S ES Ku Stacy M SM Morel Carole C Tzavaras Nikos N Montgomery Sarah E SE He Michelle M Salton Stephen R SR Russo Scott J SJ Nestler Eric J EJ Friedman Jeffrey M JM Cao Jun-Li JL Han Ming-Hu MH

Biological psychiatry 20180906 3

<h4>Background</h4>Homeostatic plasticity in mesolimbic dopamine (DA) neurons plays an essential role in mediating resilience to social stress. Recent evidence implicates an association between stress resilience and projections from the locus coeruleus (LC) to the ventral tegmental area (VTA) (LC→VTA) DA system. However, the precise circuitry and molecular mechanisms of the homeostatic plasticity in mesolimbic DA neurons mediated by the LC→VTA circuitry, and its role in conferring resilience to ...[more]

PMID: 30336931

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Dataset Information

?1- and ?3-Adrenergic Receptor-Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice.

Publications

α<sub>1</sub>- and β<sub>3</sub>-Adrenergic Receptor-Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice.

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