Cited by 169Neuroendocrine regulation and behaviorNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index; none of the 14 sources its claims cite is checked for support yet.

A prefrontal–paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in mice

Open access

Abstract

Juvenile social isolation reduces sociability in adulthood, but the underlying neural circuit mechanisms are poorly understood. We found that, in male mice, 2 weeks of social isolation immediately following weaning leads to a failure to activate medial prefrontal cortex neurons projecting to the posterior paraventricular thalamus (mPFC→pPVT) during social exposure in adulthood. Chemogenetic or optogenetic suppression of mPFC→pPVT activity in adulthood was sufficient to induce sociability deficits without affecting anxiety-related behaviors or preference toward rewarding food. Juvenile isolation led to both reduced excitability of mPFC→pPVT neurons and increased inhibitory input drive from low-threshold-spiking somatostatin interneurons in adulthood, suggesting a circuit mechanism underlying sociability deficits. Chemogenetic or optogenetic stimulation of mPFC→pPVT neurons in adulthood could rescue the sociability deficits caused by juvenile isolation. Our study identifies a pair of specific medial prefrontal cortex excitatory and inhibitory neuron populations required for sociability that are profoundly affected by juvenile social experience. Yamamuro et al. show that juvenile social isolation disrupts prefrontal neurons projecting to the paraventricular thalamus and associated prefrontal somatostatin interneurons, and thereby impairs sociability in adulthood.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In male mice, juvenile social isolation (p21–35) prevents adult recruitment of medial prefrontal cortex neurons projecting to posterior paraventricular thalamus (mPFC→pPVT) during social exposure, and manipulating this circuit bidirectionally alters sociability. The same isolation reduces mPFC→pPVT excitability and increases inhibitory drive from low-threshold spiking somatostatin interneurons, while activating mPFC→pPVT neurons rescues adult sociability deficits.

Key findings

  • Juvenile social isolation (jSI) reduced adult sociability in the 3-chamber test compared with group-housed (GH) mice (two-tailed t-test, t36=2.154, *P=0.038, n=20 GH, n=18 jSI), and mPFC→pPVT neurons were activated by a novel mouse in GH but not jSI mice.
  • Chemogenetic or optogenetic suppression of mPFC→pPVT activity in adult GH mice reduced sociability without affecting motor activity, anxiety-related behavior, or natural food preference; optogenetic activation of mPFC→pPVT projections was reinforcing and increased sociability.
  • Adult jSI mice showed reduced intrinsic excitability of mPFC→pPVT neurons and increased spontaneous inhibitory postsynaptic currents, with a significant decrease in the sEPSC/sIPSC frequency ratio; these effects emerged in adulthood, not at p35.
  • mPFC Chrna2+ LTS-SST interneurons showed increased excitability after jSI, and eDREADD activation of these interneurons in GH mice reduced sociability; chemogenetic or optogenetic activation of mPFC→pPVT neurons rescued sociability deficits in adult jSI mice, including a rescue sustained 24 hours after repeated stimulation.

Methods

  • Male C57Bl/6 wildtype, Chrna2-Cre, PV-Cre, and SST-Cre mice were used; jSI mice were isolated from weaning at p21 for two weeks, re-grouped at p35, and behaviorally tested at 10–15 weeks old.
  • Circuit activity was measured with fiber photometry (GCaMP6f), c-Fos mapping, chemogenetic (iDREADD/eDREADD) and wireless optogenetic (eNpHR3.0/ChR2) manipulations, in vivo electrophysiology, and whole-cell patch-clamp recordings in mPFC and pPVT.
  • Behavior included the 3-chamber sociability test, milkshake preference test, elevated plus maze, and open field; analyses used t-tests, 2-way ANOVAs, and paired tests as indicated.

Limitations

  • The paper states that no statistical methods were used to pre-determine sample sizes, data collection and analysis were not performed blind to conditions, and data distribution was assumed normal but not formally tested.
  • The study used male mice only, so sex differences or female sociability are not addressed (evident from the Methods).
  • Some mechanistic conclusions rely on correlational circuit changes plus acute manipulations; the paper notes future studies are needed to reveal how different mPFC projection populations influence subcortical social networks.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41593-020-0695-6

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

103 Own result · 13 Own method · 13 Own interpretation · 8 Not checked yet

Verify all 14 references — free account

Show all 76 claims

  • The quote only partly states this claim. 9
  • It may state two separate claims as one. 22
  • Probably not a substantial claim. 39
61 of 61
  • The authors state this as an assumption.

    Data distribution was assumed to be normal but this was not formally tested.

    “Data distribution was assumed to be normal but this was not formally tested.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

2 of 2

Citations

Cites

Show all 31 references

Cited by

Sorted by citations

See all 169

Metadata

Authors
Yamamuro, K., Bicks, L. K., Leventhal, M. B., Kato, D., Im, S., Flanigan, M. E., Garkun, Y., Norman, K. J., Caro, K., Sadahiro, M., Kullander, K., Akbarian, S., Russo, S. J., & Morishita, H.
Affiliations
  • Nara Medical University (JP)
  • Icahn School of Medicine at Mount Sinai (US)
  • Uppsala University (SE)
Corresponding author
Morishita, Hirofumi
Venue
Nature Neuroscience
Published
2020-08-31
Volume
23
Issue
10
Pages
1240-1252
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W3082986453
Cited by
169
References
31
Citations by year
2026: 17 · 2025: 31 · 2024: 34 · 2023: 22 · 2022: 37 · 2021: 24 · 2020: 4
FWCI
23.78
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • MEXT | Japan Society for the Promotion of Science
  • Naito Foundation
  • Uehara Memorial Foundation
  • Mochida Memorial Foundation for Medical and Pharmaceutical Research
  • U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (T32MH966785, R01MH118297, R01MH119523)
  • Simons Foundation (610850)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
medial prefrontal cortex, somatostatin interneurons, social behavior deficits, chemogenetic manipulation, optogenetic stimulation
MeSH terms
Animals, Behavior, Animal, Interneurons, Male, Neural Pathways, Neurons, Social Behavior, Social Isolation, Prefrontal Cortex, Midline Thalamic Nuclei, Optogenetics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review