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Reward integration in prefrontal-cortical and ventral-hippocampal nucleus accumbens inputs cooperatively modulates engagement

Eshaan S Iyer, Peter Vitaro, Serena Wu, Jessie Muir, Yiu Chung Tse, Vedrana Cvetkovska, Rosemary C. Bagot

2025Nature Communications14 citationsDOIOpen Access PDF

Abstract

The nucleus accumbens, a highly integrative brain region controlling motivated behavior, receives various glutamatergic inputs, yet the relative functional specialization of these inputs is unclear. While circuit neuroscience commonly seeks specificity, redundancy can be highly adaptive and is a critical motif in circuit organization. Using dual-site fiber photometry in an operant reward task in mice, we simultaneously recorded from two accumbal glutamatergic afferents to assess circuit specialization. We identify a common neural motif integrating reward history in medial prefrontal cortex and ventral hippocampus inputs. By systematically degrading task complexity, dissociating reward from choice and action, we identify circuit-specificity in the behavioral conditions that recruit encoding. While input from the prefrontal cortex invariantly encodes reward, encoding in ventral hippocampal input is uniquely anchored to unrewarded outcomes. Optogenetic stimulation demonstrates that both inputs co-operatively modulate task engagement. We illustrate how similar encoding, differentially gated by behavioral state, supports state-sensitive tuning of reward-motivated behavior. Neural circuit mechanisms underlying integrating information about reward across time are not fully understood. Here, the authors show that common outcome-integration signals from the medial prefrontal cortex and ventral hippocampus inputs interact in the nucleus accumbens to dynamically modulate task engagement.

Topics & Concepts

Nucleus accumbensNeuroscienceHippocampal formationPrefrontal cortexFunctional connectivityOptogeneticsVentral tegmental areaPsychologyBiologyDopamineCognitionDopaminergicMemory and Neural MechanismsNeural and Behavioral Psychology StudiesNeural dynamics and brain function