Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states

Mol Psychiatry. 2023 Sep;28(9):3856-3873. doi: 10.1038/s41380-023-02269-8. Epub 2023 Sep 29.


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

MeSH terms

  • Animals
  • Astrocytes* / physiology
  • Depressive Disorder, Major*
  • Humans
  • Mice
  • Serotonergic Neurons
  • Serotonin
  • Signal Transduction / physiology


  • Serotonin