Dorsal bed nucleus of the stria terminalis GABA neurons are necessary for chronic unpredictable stress-induced depressive behaviors in adolescent male mice

Abstract

Background: Previous studies have shown that neurons in the Bed Nucleus of the Stria Terminalis (BNST) respond to stress and play a key role in mental health. However, the cellular bases of BNST in adolescent depression remain elusive.

Methods: Male C57BL/6 mice were randomly assigned to the control (Ctrl) or chronic unpredictable stress (CUS) groups. The CUS mice, aged 28 days, were subjected to diverse stressors at various times of the day for 12 days. Depression-like behaviors were assessed through the sucrose preference test (SPT) and tail suspension test (TST). Immunostaining was used to investigate the neural activity and subtypes in the brain. A chemogenetic tool was conducted to examine the role of specific neural activity in CUS-induced depression-like behaviors.

Results: CUS led to a significant decrease in preference for sucrose solution in the SPT and increased immobility time in the TST. C-Fos immunostaining showed hyperactivity of the GABAergic neurons within the dorsal BNST (dBNST^GABA). Chemogenetic activation of dBNST^GABA neurons increased depression-like behaviors. Conversely, chemogenetic inhibition of dBNST^GABA neurons led to a decrease in CUS-induced depression.

Conclusions: These results suggest that adolescent CUS induces hyperactivity of dBNST^GABA neurons, subsequently giving rise to depression-like behaviors and that reducing dBNST^GABA neuronal activity might constitute a novel and efficacious therapeutic approach for adolescent depression.

Keywords: Adolescence; Chronic unpredictable stress; Depression; Dorsal bed nucleus of the stria terminalis; c-Fos.