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Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory.
dc.contributor.author | Albert Gasco, Hector | |
dc.contributor.author | García Avilés, Álvaro | |
dc.contributor.author | Moustafa, S. | |
dc.contributor.author | Sánchez-Sarasúa, Sandra | |
dc.contributor.author | Gundlach, Andrew Lawrence | |
dc.contributor.author | Olucha-Bordonau, Francisco E | |
dc.contributor.author | Sánchez-Pérez, Ana María | |
dc.date.accessioned | 2016-12-05T10:51:38Z | |
dc.date.available | 2016-12-05T10:51:38Z | |
dc.date.issued | 2016-05-05 | |
dc.identifier.citation | ALBERT GASCÓ, Héctor; GARCÍA AVILÉS, Álvaro; MOUSTAFA, S.; SÁNCHEZ SARASÚA DE LA BÁRCENA, Sandra; GUNDLANCH, Andrew L.; OLUCHA BORDONAU, Francisco E., SÁNCHEZ PÉREZ, Ana María. Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory. Brain structure & function (2016), online, pp. 1-15 | ca_CA |
dc.identifier.uri | http://hdl.handle.net/10234/164908 | |
dc.description.abstract | The medial septum/diagonal band (MS/DB) is a relay region connecting the hypothalamus and brainstem with the hippocampus, and both the MS/DB and dorsal/ventral hippocampus receive strong topographic GABA/peptidergic projections from the nucleus incertus of the pontine tegmentum. The neuropeptide relaxin-3, released by these neurons, is the cognate ligand for a Gi/o-protein-coupled receptor, RXFP3, which is highly expressed within the MS/DB, and both cholinergic and GABAergic neurons in this region of rat brain receive relaxin-3 positive terminals/boutons. Comprehensive in vitro studies have demonstrated that a range of cell signaling pathways can be altered by RXFP3 stimulation, including inhibition of forskolin-activated cAMP levels and activation of ERK phosphorylation. In this study we investigated whether intracerebroventricular (icv) injection of RXFP3-A2, a selective relaxin-3 receptor agonist, altered ERK phosphorylation levels in the MS/DB of adult male rats. In addition, we assessed the neurochemical phenotype of phosphorylated (p) ERK-positive neurons in MS/DB after RXFP3-A2 administration by dual-label immunostaining for pERK and key neuronal markers. RXFP3-A2 injection significantly increased pERK levels in MS/DB, compared to vehicle at 20 and 90 min post-injection. In addition, icv injection of RXFP3-A2 increased the number of cells expressing pERK in the MS/DB after 90 min, with increases detected in cholinergic, but not GABAergic neurons. Moreover, we found that septal cholinergic neurons express RXFP3 and that icv infusions of RXFP3-A2 impaired alternation in a spatial working memory behavioral paradigm. The presence of the receptor and the specific RXFP3-related activation of the MAPK/ERK pathway in MS/DB cholinergic neurons identifies them as a key target of ascending relaxin-3 projections with implications for the acute and chronic inhibition of cholinergic neuron activity/function by relaxin-3/RXFP3 signaling. | ca_CA |
dc.description.sponsorShip | This research was supported by a predoctoral fellowship (FPI-UJI: PREDOC/2014/35) to HAG; a traineeship fellowship (UJI P1·1A2014-06) to AGA; the FP7-PEOPLE-IRSES PIRSES-GA-2012-318997 NEUREN project to ALG and FEO-B; NHMRC (Australia) project grants (1027522, 1026939) and a Brain and Behavior Research Foundation (USA) NARSAD Independent Investigator Award to ALG; Generalitat Valenciana (AICO/2015/042) project grant and Universitat Jaume I (P1·1A2014-06) project grant to AMS. | ca_CA |
dc.format.extent | 26 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | Springer | ca_CA |
dc.relation.isPartOf | Brain structure & function (2016), online | ca_CA |
dc.rights.uri | http://rightsstatements.org/vocab/CNE/1.0/ | * |
dc.subject | Calcium-binding proteins | ca_CA |
dc.subject | Choline acetyltransferase | ca_CA |
dc.subject | GABA neurons | ca_CA |
dc.subject | MAPK/ERK pathway | ca_CA |
dc.subject | Nucleus incertus | ca_CA |
dc.subject | Septum | ca_CA |
dc.subject | Working spatial memory | ca_CA |
dc.subject | RXFP3 labeling | ca_CA |
dc.title | Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory. | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | http://dx.doi.org/10.1007/s00429-016-1227-8 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.relation.publisherVersion | https://www.ncbi.nlm.nih.gov/pubmed/27146679 | ca_CA |
dc.type.version | info:eu-repo/semantics/sumittedVersion |
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