Rivera, PatriciaArrabal, SergioCifuentes, ManuelGrondona, Jesús MPérez-Martín, MargaritaRubio, LeticiaVargas, AntonioSerrano, AntoniaPavón, Francisco JSuárez, JuanRodríguez de Fonseca, Fernando2015-12-012015-12-012014-06-27Rivera P, Arrabal S, Cifuentes M, Grondona JM, Pérez-Martín M, Rubio L, et al. 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. Front Neuroanat. 2014; 8:56http://hdl.handle.net/10668/2090Journal Article;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.enCannabinoid receptor2-arachidonoylglycerolCalcium-binding proteinHippocampusRatImmunohistochemistryConfocal microscopyÁcidos araquidónicosRegión CA1 del hipocampoCannabinoidesProteínas transportadorasGiro dentadoHipocampoRatastransmisión sinápticaMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic AcidsMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus::CA1 Region, HippocampalMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::CannabinoidsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier ProteinsMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus::Dentate GyrusMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::EndocannabinoidsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Histological Techniques::Histocytochemistry::Immunohistochemistry::Fluorescent Antibody TechniqueMedical Subject Headings::Chemicals and Drugs::Carbohydrates::GlycosidesMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::HippocampusMedical Subject Headings::Anatomy::Nervous System::Neurons::InterneuronsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Microscopy::Microscopy, ConfocalMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::NeuropilinsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Contractile Proteins::Muscle Proteins::ParvalbuminsMedical Subject Headings::Anatomy::Nervous System::Neurons::Pyramidal CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Signal Transduction::Synaptic TransmissionMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction::Synaptic TransmissionMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Calcium-Binding Proteins::Calbindinsresearch article25018703open access10.3389/fnana.2014.000561662-5129PMC4073216