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 and Rosemary C. Bagot ()
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Eshaan S. Iyer: McGill University
Peter Vitaro: McGill University
Serena Wu: McGill University
Jessie Muir: Princeton University
Yiu Chung Tse: McGill University
Vedrana Cvetkovska: McGill University
Rosemary C. Bagot: McGill University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58858-4

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