The research team led by Professor HU Hailan from the Zhejiang University School of Medicine, has recently published a groundbreaking article titled Neuron-astrocyte Coupling in Lateral Habenula Mediates Depressive-like Behaviors in Cell on April 24th, 2025. This study reveals how brain cells dynamically cooperate to drive stress response and depression.

Stress-induced depression-like behaviors are driven by a dynamic recurrent network involving neurons and astrocytes in the lateral habenula and norepinephrine release from neurons in the locus coeruleus in freely-moving mice.

LHb neuron-astrocyte synergy in depression

The lateral habenular (LHb) neurons and astrocytes have been strongly implicated in depression etiology but it was not clear how the two dynamically interact during depression onset. Here, using multi-brain-region calcium photometry recording in freely-moving mice, the research team discover that stress induces a most rapid astrocytic calcium rise and a unique bimodal neuronal response in the LHb. LHb astrocytic calcium requires the α1A-adrenergic receptor, and depends on a recurrent neural network between the LHb and locus coeruleus (LC). Through the gliotransmitter glutamate and ATP/Adenosine, LHb astrocytes mediate the second-wave LHb neuronal activation and norepinephrine (NE) release. Activation or inhibition of LHb astrocytic calcium signaling facilitates or prevents stress-induced depressive-like behaviors respectively. These results identify a stress-induced positive feedback loop in the LHb-LC axis, with astrocytes being a critical signaling relay. The identification of this prominent neuron-glia interaction may shed light on stress management and depression prevention.

Source: The research team led by Professor HU Hailan