title: Localization of the cannabinoid CB1 receptor and the 2-AG synthesizing (DAGLα) and degrading (MAGL, FAAH) enzymes in cells expressing the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus.
abstract: The retrograde suppression of the synaptic transmission by the endocannabinoid sn-2-arachidonoylglycerol (2-AG) is mediated by the cannabinoid CB1 receptors and requires the elevation of intracellular Ca(2+) and the activation of specific 2-AG synthesizing (i.e., DAGLα) enzymes. However, the anatomical organization of the neuronal substrates that express 2-AG/CB1 signaling system-related molecules associated with selective Ca(2+)-binding proteins (CaBPs) is still unknown. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the expression of the 2-AG/CB1 signaling system (CB1 receptor, DAGLα, MAGL, and FAAH) and the CaBPs calbindin D28k, calretinin, and parvalbumin in the rat hippocampus. CB1, DAGLα, and MAGL labeling was mainly localized in fibers and neuropil, which were differentially organized depending on the hippocampal CaBPs-expressing cells. CB(+) 1 fiber terminals localized in all hippocampal principal cell layers were tightly attached to calbindin(+) cells (granular and pyramidal neurons), and calretinin(+) and parvalbumin(+) interneurons. DAGLα neuropil labeling was selectively found surrounding calbindin(+) principal cells in the dentate gyrus and CA1, and in the calretinin(+) and parvalbumin(+) interneurons in the pyramidal cell layers of the CA1/3 fields. MAGL(+) terminals were only observed around CA1 calbindin(+) pyramidal cells, CA1/3 calretinin(+) interneurons and CA3 parvalbumin(+) interneurons localized in the pyramidal cell layers. Interestingly, calbindin(+) pyramidal cells expressed FAAH specifically in the CA1 field. The identification of anatomically related-neuronal substrates that expressed 2-AG/CB1 signaling system and selective CaBPs should be considered when analyzing the cannabinoid signaling associated with hippocampal functions.
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental) Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental) Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Arrabal
authors.affiliation: Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga Málaga, Spain ; CIBER BBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cifuentes
authors.affiliation: Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga Málaga, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Grondona
authors.affiliation: Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga Málaga, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Pérez-Martín
authors.affiliation: Departamento de Anatomía y Medicina Legal, Facultad de Medicina, Universidad de Málaga Málaga, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Rubio
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental) Málaga, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vargas
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental) Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación Madrid, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental) Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pavón
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental) Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.affiliation: Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental) Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
keywords: 2-arachidonoylglycerol; calcium-binding protein; cannabinoid receptor; confocal microscopy; hippocampus; immunohistochemistry; rat