Evidence map›Paper›PMID 40894021›Full record

ArticleResearch square2025

A novel and evolutionarily conserved inhibitory circuit selectively regulates dentate gyrus mossy cell function.

Geoffrey A Vargish, Haley Rice, Xiaoqing Yuan, Steven Hunt, Adam P Caccavano, Brendan E Hines, Anya Plotnikova, Arya Mohanty, Elisabetta Furlanis, Yating Wang and 10 more

Abstract readPreprint
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Geoffrey A VargishEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Section on Cellular and Synaptic Physiology, National Institutes of Health (NIH), Bethesda, MD 20892 USA.
Haley RiceEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Section on Cellular and Synaptic Physiology, National Institutes of Health (NIH), Bethesda, MD 20892 USA.
Xiaoqing YuanEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Section on Cellular and Synaptic Physiology, National Institutes of Health (NIH), Bethesda, MD 20892 USA.
Steven HuntEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Section on Cellular and Synaptic Physiology, National Institutes of Health (NIH), Bethesda, MD 20892 USA.
Adam P CaccavanoEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Section on Cellular and Synaptic Physiology, National Institutes of Health (NIH), Bethesda, MD 20892 USA.
Brendan E HinesNational Institute of Mental Health (NIMH), NIH, Bethesda, MD 20892 USA.
Anya PlotnikovaNational Institute of Mental Health (NIMH), NIH, Bethesda, MD 20892 USA.
Arya MohantyNational Institute of Mental Health (NIMH), NIH, Bethesda, MD 20892 USA.
Elisabetta FurlanisHarvard Medical School, Blavatnik Institute, Department of Neurobiology, Boston, MA 02115 USA.
Yating WangHarvard Medical School, Blavatnik Institute, Department of Neurobiology, Boston, MA 02115 USA.ORCID 0000-0002-2030-6176
Min DaiHarvard Medical School, Blavatnik Institute, Department of Neurobiology, Boston, MA 02115 USA.ORCID 0000-0001-7584-5014
Brenda Leyva GarciaHarvard Medical School, Blavatnik Institute, Department of Neurobiology, Boston, MA 02115 USA.
Alex C CumminsNational Institute of Mental Health (NIMH), NIH, Bethesda, MD 20892 USA.
Mark A G EldridgeNewcastle University, Newcastle, UK.
Bruno B AverbeckNational Institute of Mental Health (NIMH), NIH, Bethesda, MD 20892 USA.ORCID 0000-0002-3976-8565
Kareem A ZaghloulNational Institute of Neurological Disease and Stroke, Intramural Research Program, NIH, Bethesda, MD 20892 USA.ORCID 0000-0001-8575-3578
Jordane DimidschsteinStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142 USA.
Gord FishellHarvard Medical School, Blavatnik Institute, Department of Neurobiology, Boston, MA 02115 USA.ORCID 0000-0002-9640-9278
Kenneth A PelkeyEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Section on Cellular and Synaptic Physiology, National Institutes of Health (NIH), Bethesda, MD 20892 USA.ORCID 0000-0002-9731-1336
Chris J McBainEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Section on Cellular and Synaptic Physiology, National Institutes of Health (NIH), Bethesda, MD 20892 USA.ORCID 0000-0002-5909-0157

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mammalian dentate gyrus contributes to mnemonic function by parsing similar events and places. The disparate activity patterns of mossy cells and granule cells are believed to enable this function yet the mechanisms that drive this circuit dynamic remain elusive. We identified a novel inhibitory interneuron subtype, characterized by VGluT3 expression, with overwhelming target selectivity for mossy cells while also revealing that CCK, PV, SST and VIP interneurons preferentially innervate granule cells. Leveraging pharmacology and novel enhancer viruses, we find that this target-specific inhibitory innervation pattern is evolutionarily conserved in non-human primates and humans. In addition, in vivo chemogenetic manipulation of VGluT3+ interneurons selectively alters the activity and functional properties of mossy cells. These findings establish that mossy cells and granule cells have unique, evolutionarily conserved inhibitory innervation patterns and suggest selective inhibitory circuits may be necessary to maintain DG circuit dynamics and enable pattern separation across species.

Identifiers

PMID40894021
PMCPMC12393461

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.