GABAergic neurons in medial prefrontal cortex and ventral hippocampus encode information about reward history in male...

Prevailing views of reward encoding focus on excitatory neurons with GABAergic interneurons relegated to a supporting role, overlooking their potential to independently encode information. Here we simultaneously examine reward encoding in GABAergic interneurons in medial prefrontal cortex (mPFC) and ventral hippocampus (vHip) in male mice, regions in which glutamatergic neurons integrate outcomes to modulate task engagement. We find a common state-sensitive encoding motif in GABAergic neurons whereby relative suppression of neural activity maps onto outcome history. Decomposing behavior into bouts of exploration and exploitation, we find that exploration gates encoding of outcome history in both mPFC and vHip GABAergic neurons. Globally, interneuron activity in both regions predicted engagement independent of state, but choice prediction was state-dependent and distributed between mPFC and vHip. Overall, these findings indicate that GABAergic neurons also participate in outcome encoding, with behavioral state shaping their role in reward-processing circuits guiding reward-motivated behavior.