Combined Social and Spatial Coding in a Descending Projection from the Prefrontal Cortex
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Abstract
Social behaviors are crucial to all mammals. Although the prelimbic cortex (PL, part of medial prefrontal cortex) has been implicated in social behavior, it is not clear which neurons are relevant or how they contribute. We found that PL contains anatomically and molecularly distinct subpopulations that target three downstream regions that have been implicated in social behavior: the nucleus accumbens (NAc), amygdala, and ventral tegmental area. Activation of NAc-projecting PL neurons (PL-NAc), but not the other subpopulations, decreased the preference for a social target. To determine what information PL-NAc neurons convey, we selectively recorded from them and found that individual neurons were active during social investigation, but only in specific spatial locations. Spatially specific manipulation of these neurons bidirectionally regulated the formation of a social-spatial association. Thus, the unexpected combination of social and spatial information within the PL-NAc may contribute to social behavior by supporting social-spatial learning.
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The mPFC is a key hub for emotional regulation and stress adaptation.
“The medial prefrontal cortex (mPFC) is a key hub for emotional regulation and stress adaptation [9, 11].”
From A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors (2026) · cites this paper as [11]
The Abstract describes the medial prefrontal cortex’s prelimbic region in social behavior and social-spatial learning, not emotional regulation or stress adaptation. Searches for those terms and for anxiety-related language found no passage in the paper’s text supporting the attributed claim; an anxiety-related study appears only in the References. (LLM, conf=0.74)
Experimental — accuracy not yet measuredActivation of NAc-projecting PL neurons, but not other subpopulations, decreases preference for a social target.
“Activation of NAc-projecting PL neurons, but not the other subpopulations, decreases the preference for a social target 32.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [32]
Activation of inputs from the prelimbic cortex to the nucleus accumbens core reduced sociability.
“Additional confusion is provided by the observation that activation of inputs from the prelimbic cortex to the NAc core reduced sociability [67].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [67]
Prior investigations in rodents and primates have provided evidence for neurons that encode information about other individuals, demonstrating changes in activity when animals observe another's appetitive or aversive experiences.
“Prior investigations in rodents and primates, for example, have provided evidence for the presence of neurons that encode information about other individuals, demonstrating changes in activity when the animals observe another’s appetitive or aversive experiences 1–11.”
From Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time (2021) · cites this paper as [10]
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References 89 · Cited by 311
- Authors
- Murugan, M., Jang, H. J., Park, M., Miller, E. M., Cox, J., Taliaferro, J. P., Parker, N. F., Bhave, V., Hur, H., Liang, Y., Nectow, A. R., Pillow, J. W., & Witten, I. B.
- Affiliations
- Princeton University (US)
- Rockefeller University (US)
- Corresponding author
- Witten, Ilana B.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 171
- Issue
- 7
- Pages
- 1663-1677.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5889923
- OpenAlex
- W2672878424
- Cited by
- 311
- References
- 89
- Citations by year
- 2026: 30 · 2025: 40 · 2024: 40 · 2023: 38 · 2022: 42 · 2021: 38 · 2020: 37 · 2019: 25 · 2018: 18 · 2017: 1 · 2016: 1
- FWCI
- 12.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pew
- McKnight
- Sloan Foundation
- NIH (DP2 DA035149-01, 5R01MH106689-02, 1F32MH112320-01A1)
- SCGB (412733)
- NSF GRFP
- NARSAD
- NCATS NIH CTSA (UL1 TR001866)
- McKnight Foundation
- Simons Collaboration on the Global Brain (SCGB AWD1004351)
- NSF CAREER Award (IIS-1150186)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- prelimbic cortex, medial prefrontal cortex, nucleus accumbens, social behavior, spatial coding, social coding, neuronal subpopulations, social investigation, social preferences, ventral tegmental area, amygdala, descending projections, single-unit recording
- MeSH terms
- Amygdala, Animals, Learning, Limbic System, Neural Pathways, Neurons, Nucleus Accumbens, Social Behavior, Spatial Behavior, Prefrontal Cortex, Ventral Tegmental Area, Mice
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