Accumbal calcium-permeable AMPA receptors orchestrate neuronal ensembles underlying social attachment

Social attachments are vital to mammalian health, but the neural microcircuitry underlying their formation remains unknown. Using prairie voles-which form lasting pair bonds-we investigate how the microcircuitry of the nucleus accumbens (NAc) transforms social interaction into attachment. We confirm that accumbal calcium-permeable AMPARs (CP-AMPARs) mediate excitation of fast-spiking interneurons (FSIs) in voles, and find that their blockade prevents pair bond formation. To understand the underlying CP-AMPAR-dependent circuit computations, we combine in vivo calcium imaging with local pharmacology. This reveals that social information is differentially encoded at neuronal and ensemble levels, with bonding leading to an emergence of partner-selective ensembles. CP-AMPAR blockade produces a striking dissociation: it disrupts partner ensemble formation while paradoxically increasing the proportion of partner-selective neurons. Further, blockade selectively impairs ensemble-level decoding, suggesting that temporally structured coactivity is essential for transmitting bonding-related information. Finally, as CP-AMPARs mediate FSI activity, we use in-vivo electrophysiology to show that FSIs dynamically and distributively coordinate medium spiny neuron (MSN) ensemble activity. Our findings delineate an accumbal microcircuit mechanism whereby ensemble formation, gated by CP-AMPARs, transforms social interactions into attachment.

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Publication Details

Journal
Nature Communications
Published
2026-01-07
DOI
https://doi.org/10.1038/s41467-025-67459-0
Primary Topic
Neuroendocrine regulation and behavior
Type
article
Field-Weighted Citation Impact
0.00

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article

Accumbal calcium-permeable AMPA receptors orchestrate neuronal ensembles underlying social attachment

William M. Sheeran, Mostafa El-Kalliny, Liza E. Brusman, Charles Hoeffer et al.
Nature Communications
Neuroendocrine regulation and behavior
article

Accumbal calcium-permeable AMPA receptors orchestrate neuronal ensembles underlying social attachment

William M. Sheeran, Mostafa El-Kalliny, Liza E. Brusman, Charles Hoeffer, Kelly E. Winther, Michael Kelberman, Olivia E. Neilly, Zoe R. Donaldson, J. Keenan Kushner
article en

Abstract

Social attachments are vital to mammalian health, but the neural microcircuitry underlying their formation remains unknown. Using prairie voles-which form lasting pair bonds-we investigate how the microcircuitry of the nucleus accumbens (NAc) transforms social interaction into attachment. We confirm that accumbal calcium-permeable AMPARs (CP-AMPARs) mediate excitation of fast-spiking interneurons (FSIs) in voles, and find that their blockade prevents pair bond formation. To understand the underlying CP-AMPAR-dependent circuit computations, we combine in vivo calcium imaging with local pharmacology. This reveals that social information is differentially encoded at neuronal and ensemble levels, with bonding leading to an emergence of partner-selective ensembles. CP-AMPAR blockade produces a striking dissociation: it disrupts partner ensemble formation while paradoxically increasing the proportion of partner-selective neurons. Further, blockade selectively impairs ensemble-level decoding, suggesting that temporally structured coactivity is essential for transmitting bonding-related information. Finally, as CP-AMPARs mediate FSI activity, we use in-vivo electrophysiology to show that FSIs dynamically and distributively coordinate medium spiny neuron (MSN) ensemble activity. Our findings delineate an accumbal microcircuit mechanism whereby ensemble formation, gated by CP-AMPARs, transforms social interactions into attachment.

Nature CommunicationsVol. 17(1)
University of Colorado Boulder (US), Donaldson (United States) (US), University of Colorado Denver (US)
National Science Foundation, National Institutes of Health, University of Colorado Boulder
Reduced inequalities
Openalex Percentile: Top 97%
Neuroendocrine regulation and behavior
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