Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states

• DOI: 10.1038/s41380-023-02269-8
• Publication Date: 2023-09-29T08:02:09Z
• Authors: Candela González-...; Andrea Sánchez-Ruiz; Julio Esparza; Cristina Sánchez-...; Lucia Arancibia; Jorge Ramírez-Franco; Davide Gobbo; Frank Kirchhoff; Gertrudis Perea

Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal synaptic physiology. Astrocytic alterations have been found Major Depressive Disorder (MDD) patients; however, the consequences astrocyte Ca2+ signaling MDD poorly understood. Here, we that corticosterone-treated juvenile mice (Cort-mice) showed altered astrocytic dynamics mPFC both resting conditions during social interactions, line with behavior. Additionally, Cort-mice displayed reduced serotonin (5-HT)-mediated astrocytes, aberrant 5-HT-driven plasticity layer 2/3 neurons. Downregulation naïve animals mimicked deficits Cort-mice. Remarkably, boosting Gq-DREADDS restored to control levels mood cognitive abilities This study highlights important role for homeostatic circuits behavior, but also reveals its potential therapeutic value depressive-like states.