학술논문

Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice
Document Type
article
Source
Nature Communications. 14(1)
Subject
Biological Psychology
Pharmacology and Pharmaceutical Sciences
Biomedical and Clinical Sciences
Psychology
Brain Disorders
Mental Health
Depression
Behavioral and Social Science
Basic Behavioral and Social Science
Neurosciences
2.1 Biological and endogenous factors
Aetiology
Good Health and Well Being
Mice
Male
Animals
Corticotropin-Releasing Hormone
Reward
Nucleus Accumbens
Basolateral Nuclear Complex
gamma-Aminobutyric Acid
Language
Abstract
Disrupted operations of the reward circuit underlie major emotional disorders, including depression, which commonly arise following early life stress / adversity (ELA). However, how ELA enduringly impacts reward circuit functions remains unclear. We characterize a stress-sensitive projection connecting basolateral amygdala (BLA) and nucleus accumbens (NAc) that co-expresses GABA and the stress-reactive neuropeptide corticotropin-releasing hormone (CRH). We identify a crucial role for this projection in executing disrupted reward behaviors provoked by ELA: chemogenetic and optogenetic stimulation of the projection in control male mice suppresses several reward behaviors, recapitulating deficits resulting from ELA and demonstrating the pathway's contributions to normal reward behaviors. In adult ELA mice, inhibiting-but not stimulating-the projection, restores typical reward behaviors yet has little effect in controls, indicating ELA-induced maladaptive plasticity of this reward-circuit component. Thus, we discover a stress-sensitive, reward inhibiting BLA → NAc projection with unique molecular features, which may provide intervention targets for disabling mental illnesses.