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Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was funded by Ministerio de Ciencia, Innovacion y Universidades, the Agencia Estatal de Investigacion (AEI) and the European Regional Development Fund (ERDF) PID2019-106332 GB-I00, the support of the Universitat Rovira i Virgili (URV) (2017PFR-URV-B2-85), and the Catalan Government (2017SGR704). LJ has been supported by the Universitat Rovira i Virgili (URV) under the framework of the "Programa Marti i Franques d'ajuts a la investigacio. Contractes de personal investigador predoctoral en formacio (PMF-PIPF)." AP has been supported by the Spanish Ministerio de Ciencia Innovacion y Universidades (Grant no. PRE2020-092084, project no. PID2019-106332 GB-I00). VC and MD were supported by a grant from MINECO under the framework of the Sistema Nacional de Garantia Juvenil, the European Social Fund (ESF) and the Iniciativa de Empleo Juvenil (IEJ) reference codes: LE1511314-2014PEJ-04 and LE1911587-2019PEJ-04. M.BS: Research Grant (FI, 2021-FI-B00755 Agencia de Gestio d'Ajuts Universitat i Recerca (AGAUR).

Analysis of institutional authors

Garcia, NCorresponding AuthorLanuza, MaAuthorTomas, MAuthorCilleros-Mane, VAuthorJust-Borras, LAuthorPolishchuk, AAuthorBalanya-Segura, MAuthorTomas, JCorresponding Author

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Article

Involvement of the Voltage-Gated Calcium Channels L- P/Q- and N-Types in Synapse Elimination During Neuromuscular Junction Development

Publicated to:Molecular Neurobiology. 59 (7): 4044-4064 - 2022-07-01 59(7), DOI: 10.1007/s12035-022-02818-2

Authors: Garcia, Neus; Hernandez, Pablo; Lanuza, Maria A; Tomas, Marta; Cilleros-Mane, Victor; Just-Borras, Laia; Duran-Vigara, Maria; Polishchuk, Aleksandra; Balanya-Segura, Marta; Tomas, Josep

Affiliations

Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. - Author
Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. josepmaria.tomas@urv.cat. - Author
Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. mariadelesneus.garcia@urv.cat. - Author
Univ Rovira & Virgili, Fac Med & Ciencies Salut, Unitat Histol & Neurobiol UHNEUROB, St Llorenc 21, Reus 43201, Spain - Author

Abstract

During the nervous system development, synapses are initially overproduced. In the neuromuscular junction (NMJ) however, competition between several motor nerve terminals and the synapses they made ends with the maturation of only one axon. The competitive signaling between axons is mediated by the differential activity-dependent release of the neurotransmitter ACh, co-transmitters, and neurotrophic factors. A multiple metabotropic receptor-driven downstream balance between PKA and PKC isoforms modulates the phosphorylation of targets involved in transmitter release and nerve terminal stability. Previously, we observed in the weakest endings on the polyinnervated NMJ that M1 mAChR receptors reduce ACh release through the PKC pathway coupled to an excess of Ca2+ inflow through P/Q- N- and L-type voltage-gated calcium channels (VGCC). This signaling would contribute to the elimination of this nerve terminal. Here, we investigate the involvement of the P/Q-, N-, and L-subtype channels in transgenic B6.Cg-Tg (Thy1-YFP)16-Jrs/J mice during synapse elimination. Then, the axon number and postsynaptic receptor cluster morphologic maturation were evaluated. The results show that both L- and P/Q-type VGCC (but not the N-type) are equally involved in synapse elimination. Their normal function favors supernumerary axonal loss by jointly enhancing intracellular calcium [Ca2+]i. The block of these VGCCs or [Ca2+]i  i sequestration results in the same delay of axonal loss as the cPKCβI and nPKCε isoform block or PKA activation. The specific block of the muscle cell's contraction with μ-conotoxin GIIIB also delays synapse maturation, and thus, a retrograde influence from the postsynaptic site regulating the presynaptic CaV1.3 may contribute to the synapse elimination.© 2022. The Author(s).

Keywords

acetylcholine-releaseadenosine a(2a)axonal competitionca2+ channelmuscarinic autoreceptorsneurotransmitter releasepostnatal synapse eliminationprotein kinasesreceptorsskeletal-muscletransmitter releasevgccweak inputsAnimalsAxonal competitionAxonsCalciumCalcium channelsMiceMotor endplateNeuromuscular junctionPostnatal synapse eliminationProtein isoformsProtein kinasesProtein-kinase-cSignal transductionSynapsesVgcc

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Molecular Neurobiology due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Neurology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.1, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-23, the following number of citations:

  • WoS: 6
  • Scopus: 6
  • Europe PMC: 5
  • OpenCitations: 5

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-23:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 18.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 18 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.5.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/20.500.11797/imarina9261806

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Garcia Sancho, Maria de les Neus) and Last Author (Tomás Ferré, José Maria).

the authors responsible for correspondence tasks have been Garcia Sancho, Maria de les Neus and Tomás Ferré, José Maria.