Cortical astrocytes flexibly encode reward contingencies and shape conditioned behavior.

Area of Science:

• Neuroscience
• Cell Biology
• Behavioral Science

Background:

• Learned associations between environmental cues and rewards are crucial for motivated behavior.
• The specific cell types supporting this learning process, particularly in the prefrontal cortex, are not fully understood.

Purpose of the Study:

• To investigate the role of dorsal medial prefrontal cortical astrocytes in the acquisition, expression, and reversal of Pavlovian conditioning.
• To determine how astrocytic activity encodes cue-reward associations and influences motivated behavior.

Main Methods:

• Longitudinal two-photon calcium imaging in mice to track astrocyte activity during Pavlovian sucrose conditioning.
• Behavioral analysis of conditioned reward seeking.
• Astrocytic ablation to assess functional necessity.

Main Results:

• Astrocytes exhibited time-locked, coordinated calcium signals that distinguished correct actions from mistakes.
• Astrocytic activity evolved to selectively represent cue-reward associations.
• Prefrontal astrocytes responded specifically to the cue-reward association, not the cue or reward alone.
• Astrocytic activity rapidly adapted to reversed reward contingencies.
• Astrocytic ablation impaired initial learning and persistence of conditioned reward seeking.

Conclusions:

• Dorsal medial prefrontal cortical astrocytes are functionally plastic and play a critical role in encoding cue-reward associations.
• These astrocytes dynamically regulate reward-seeking behavior throughout learning and adaptation to changing contingencies.