Astrocytes Control Cocaine-Induced Synaptic Plasticity and Reward Through the Matricellular Protein Hevin
Raphaële Mongrédien1, Augusto Anesio2, Gustavo J D Fernandes2
1Sorbonne Université, INSERM, CNRS, Neuroscience Paris Seine, Paris, France.
Biological Psychiatry
|March 20, 2025
Summary
Cocaine alters astrocyte calcium (Ca2+) signals in the nucleus accumbens, which are essential for developing cocaine-seeking behavior. The protein hevin mediates these effects on reward and neuronal plasticity.
Area of Science:
- Neuroscience
- Cellular Biology
- Neuropharmacology
Background:
- Astrocytes in the nucleus accumbens (NAc) modulate glutamatergic neurotransmission, influencing synaptic plasticity related to drug addiction.
- Astrocyte-derived factors may contribute to brain circuitry changes driving drug-seeking behavior.
Purpose of the Study:
- To investigate the role of astrocyte calcium (Ca2+) signals in vivo and the secreted protein hevin in the rewarding effects of cocaine.
Main Methods:
- In vivo fiber photometry measured NAc astrocyte Ca2+ signals during cocaine-conditioned place preference (CPP).
- Chemogenetics and Ca2+ depletion assessed astrocyte Ca2+ signal contributions to cocaine CPP.
- Hevin-null mice and hevin knockdown in NAc astrocytes were studied using spine imaging, electrophysiology, and CPP.
Main Results:
- Cocaine exposure increased NAc astrocyte Ca2+ signal amplitude.
- Modulating astrocyte Ca2+ signals altered cocaine CPP acquisition.
- Hevin knockdown in NAc astrocytes reduced cocaine-induced CPP and neuronal plasticity.
Conclusions:
- Cocaine fine-tunes NAc astrocyte Ca2+ signals, which are critical for cocaine-seeking behavior.
- Astrocyte-released hevin is a key mediator of cocaine's effects on reward and neuronal plasticity.
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