Astrocyte ensembles manipulated with AstroLight tune cue-motivated behavior

Abstract

Astrocytes, dynamic cells crucial to brain function, have traditionally been overshadowed by the emphasis on neuronal activity in regulating behavior. Unlike neurons, which are organized into ensembles that encode different brain representations, astrocytes have long been considered a homogeneous population. This is partly because of the lack of tools available to map and manipulate specific subsets of astrocytes based on their functional activity, obscuring the extent of their specialization in circuits. Here, using AstroLight, a tool that translates astrocytic activity-mediated calcium signals into gene expression in a light-dependent manner, we have identified an astrocytic ensemble, a functionally specified subset of astrocytes that emerges upon activity during cue-motivated behaviors in the nucleus accumbens, an integrator hub in the reward system. Furthermore, through gain-of-function and loss-of-function manipulations, we demonstrate that this ensemble is essential for modulating cue–reward associations. These findings highlight the specialization of astrocytes into ensembles and their fine-tuning role in shaping salient behavior.