Developmental regulation of GABAB receptors and downstream molecules in the mouse brain

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dc.contributor.authorAna Fajardo Serrano
dc.contributor.authorRocío Alfaro Ruiz
dc.contributor.authorMaría Llanos Martínez Poyato
dc.contributor.authorAna Esther Moreno-Martínez
dc.contributor.authorSebastián García Madrona
dc.contributor.authorAlberto Roldán Sastre
dc.contributor.authorPablo Alonso-Gómez
dc.contributor.authorMiriam Fernández
dc.contributor.authorRicardo Puertas-Avendaño
dc.contributor.authorRyuichi Shigemoto
dc.contributor.authorKirill A. Martemyanov
dc.contributor.authorRafael Luján
dc.contributor.authorCarolina Aguado
dc.contributor.departmentBiología Celular e Histología
dc.date.accessioned2025-11-11T08:23:45Z
dc.date.available2025-11-11T08:23:45Z
dc.date.issued2025
dc.description.abstractMetabotropic GABA (GABAB) receptors have modulatory functions on neuronal excitability and neurotransmitter release. To fulfil these functions, GABAB receptors form macromolecular signaling complexes with G proteins, effectors, and other associated proteins. Here we investigated the postnatal development of GABAB receptors (GABAB1 and GABAB2 subunits) in mouse brain, focusing on potential similarities in the spatial and temporal expression pattern of their associated proteins CaV2.1, Gαo, Gβ5, and RGS7, using histoblots, immunofluorescence, and immunoelectron microscopic techniques. At all ages analyzed, histoblot showed that the six proteins were widely expressed in the brain, with mostly an overlapping pattern throughout postnatal development. In the hippocampus, immunoelectron microscopy and quantitative analysis of immunoparticles for GABAB1, GABAB2, Gαo, Gβ5, and RGS7 revealed their progressive enrichment around excitatory synapses on dendritic spines of CA1 pyramidal cells toward P15. At presynaptic sites, GABAB receptors colocalize with CaV2.1, Gαo, Gβ5, and RGS7 in the active zone and extrasynaptic membranes of axon terminals, establishing synapses on dendritic spines of CA1 pyramidal cells. In the cerebellum, double immunofluorescence at P7 and P10 revealed the colocalization of GABAB1 and CaV2.1 in the whole dendritic tree of developing Purkinje cells. Immunoelectron microscopy at P15 showed that GABAB1, GABAB2, CaV2.1, Gαo, Gβ5, and RGS7 are distributed along the dendritic surface of Purkinje cells, enriched close to excitatory synapses in spines. Altogether, these data suggest that macromolecular complexes composed of GABAB1 /GABAB2/CaV2.1/ Gαo/Gβ5/RGS7 are pre-assembled during key stages of postnatal development in hippocampal and cerebellar neurons.
dc.formatapplication/pdf
dc.format.extent18
dc.identifier.doihttps://doi.org/10.14670/HH-18-970
dc.identifier.eissn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/172049
dc.languageeng
dc.relationSin financiacion externa a la Universidad
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHippocampus
dc.subjectCerebellum
dc.subjectGABAB receptors
dc.subjectG proteins
dc.subjectCalcium channels
dc.subjectHistoblot
dc.subjectElectron microscopy
dc.subjectPostnatal development
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleDevelopmental regulation of GABAB receptors and downstream molecules in the mouse brain
dc.typeinfo:eu-repo/semantics/article
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Histology and histopathology, Vol.40, Nº12, (2025)