AN ASTROCYTE ENSEMBLE MODULATES SYNAPTIC COMMUNICATION IN THE MEDIAL PREFRONTAL CORTEX-NUCLEUS ACCUMBENS CIRCUIT

Astrocytes have long been acknowledged as active participants in synaptic communication. Although their role in the tripartite synapse is established, they have traditionally been assumed to work in unison. However, accumulating evidence shows that astrocytes activate in the form of sparse groups, or astrocyte ensembles. The nucleus accumbens (NAc), a central hub of the reward system of the brain, receives and integrates multiple glutamatergic inputs for reward processing. These afferents from different brain regions have been shown to activate distinct astrocyte ensembles. If and how these ensembles integrate into NAc circuits and affect network function remains unexplored. Here, we obtained a three-dimensional map of the accumbal astrocyte ensemble activated by the medial prefrontal cortex (mPFC). Using a combination of patch clamp electrophysiology, imaging, astrocyte tagging, and histological techniques, we explore gap junction coupling as a possible mechanism driving the recruitment of astrocytes to the ensemble. We employ AstroLight, a tool for calcium and light-dependent gene expression in active astrocytes, to manipulate this astrocyte ensemble, showing that it is involved in long-term depression of mPFC-NAc synapses. Altogether, these results shed light on the mechanisms by which distinct astrocyte ensembles interweave in brain circuits and modulate information flow within the NAc.