Evidence map›Paper›PMID 40728771›Full record

ArticleMolecular neurobiology2025

Necl-4/CADM4 regulates GABAergic synaptic strength on GABAergic inhibitory neurons via ErbB4 activation and prevents neuronal impairments.

Ryouhei Komaki, Hajime Shiotani, Toshihiko Kuriu, Takeshi Kameyama, Muneaki Miyata, Shin Kedashiro, Kimitaka Katanazaka, Shota Nishii, Norio Chihara, Riki Matsumoto and 4 more

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In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

What it found

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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

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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

1 citing paper in PubMed.

  1. Article
4 · The record

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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

14 authors.

Ryouhei KomakiDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan.
Hajime ShiotaniDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan.
Toshihiko KuriuCenter for Medical Research and Development, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, 569-8686, Japan.
Takeshi KameyamaDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan.
Muneaki MiyataDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan.
Shin KedashiroDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan.
Kimitaka KatanazakaDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan.
Shota NishiiDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan.
Norio ChiharaDivision of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0017, Japan.
Riki MatsumotoDivision of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0017, Japan.
Michinori KoebisSection of Animal Research and Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
Atsu AibaSection of Animal Research and Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
Kiyohito MizutaniDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan. kiyohito_mizutani@tokushima-u.ac.jp.
Yoshimi TakaiDivision of Pathogenetic Signaling, Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0047, Japan. ytakai@med.kobe-u.ac.jp.

Funding

Japan Agency for Medical Research and Development JP22gm1710005Japan Science and Technology Agency JPMJPF2018Japan Society for the Promotion of Science JP21K06410Japan Society for the Promotion of Science JP22K15213Japan Society for the Promotion of Science JP22KJ2273
6 · The paper itself

Abstract

Neural networks comprise excitatory and inhibitory neurons, linked through excitatory and inhibitory synapses. Synaptic excitation/inhibition balance is controlled for brain development and functions, and its dysregulations are implicated in aging-dependent neuronal impairments. Here, we found that Necl-4/CADM4, an immunoglobulin superfamily cell adhesion molecule, is expressed in γ-aminobutyric acidergic (GABAergic) inhibitory neurons and localizes at GABAergic synapses on inhibitory neurons in cultured hippocampal neurons and the mouse hippocampus. Necl-4 genetic ablation induced neuronal loss with synaptic degenerations in the hippocampus, and cultured Necl-4-knockout (KO) hippocampal neurons were more susceptible to death. Prior to the neuronal death, the Necl-4-KO hippocampal neurons showed an increase in GABAergic synapse density on inhibitory neurons and in synaptic molecules at GABAergic synapses on inhibitory neurons, which were regulated by ErbB4 activation. Furthermore, electrophysiological analysis revealed that Necl-4 genetic ablation enhanced GABAergic synaptic currents on inhibitory neurons and induced high-frequency firing in dissociated hippocampal cultures composed of glutamatergic excitatory neurons and inhibitory neurons, contributing to excitotoxicity-mediated neuronal death. Thus, Necl-4 regulates GABAergic synaptic strength on inhibitory neurons via ErbB4 activation and prevents neuronal impairments.

Indexed as

GABAergic NeuronsNeural InhibitionReceptor, ErbB-4SynapsesAnimalsCell DeathCells, Culturedgamma-Aminobutyric AcidHippocampusMiceMice, Inbred C57BLMice, KnockoutErbb4 protein, mousegamma-Aminobutyric AcidReceptor, ErbB-4ErbB4GABAergic synapsesGABA receptorInhibitory neuronNecl-4/CADM4Neuronal impairments

Identifiers

PMID40728771
PMCPMC12559063

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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.