title: Anatomical characterization of the cannabinoid CB1receptor in cell-type-specific mutant mouse rescue models.
abstract: Type 1 cannabinoid (CB1) receptors are widely distributed in the brain. Their physiological roles depend on their distribution pattern, which differs remarkably among cell types. Hence, subcellular compartments with little but functionally relevant CB1receptors can be overlooked, fostering an incomplete mapping. To overcome this, knockin mice with cell-type-specific rescue of CB1receptors have emerged as excellent tools for investigating CB1receptors' cell-type-specific localization and sufficient functional role with no bias. However, to know whether these rescue mice maintain endogenous CB1receptor expression level, detailed anatomical studies are necessary. The subcellular distribution of hippocampal CB1receptors of rescue mice that express the gene exclusively in dorsal telencephalic glutamatergic neurons (Glu-CB1-RS) or GABAergic neurons (GABA-CB1-RS) was studied by immunoelectron microscopy. Results were compared with conditional CB1receptor knockout lines. As expected, CB1immunoparticles appeared at presynaptic plasmalemma, making asymmetric and symmetric synapses. In the hippocampal CA1 stratum radiatum, the values of the CB1receptor-immunopositive excitatory and inhibitory synapses were Glu-CB1-RS, 21.89% (glutamatergic terminals); 2.38% (GABAergic terminals); GABA-CB1-RS, 1.92% (glutamatergic terminals); 77.92% (GABAergic terminals). The proportion of CB1receptor-immunopositive excitatory and inhibitory synapses in the inner one-third of the dentate molecular layer was Glu-CB1-RS, 53.19% (glutamatergic terminals); 2.30% (GABAergic terminals); GABA-CB1-RS, 3.19% (glutamatergic terminals); 85.07% (GABAergic terminals). Taken together, Glu-CB1-RS and GABA-CB1-RS mice show the usual CB1receptor distribution and expression in hippocampal cell types with specific rescue of the receptor, thus being ideal for in-depth anatomical and functional investigations of the endocannabinoid system. J. Comp. Neurol. 525:302-318, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Neurosciences, University of the Basque Country UPV/EHU, E-48940, Leioa, Spain.|Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, 48170, Zamudio, Spain.|Université de Bordeaux, Bordeaux, F-33076, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez-Rodríguez
authors.affiliation: Department of Neurosciences, University of the Basque Country UPV/EHU, E-48940, Leioa, Spain.|Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, 48170, Zamudio, Spain.
authors.forename: Nagore
authors.initials: N
authors.lastname: Puente
authors.affiliation: Department of Neurosciences, University of the Basque Country UPV/EHU, E-48940, Leioa, Spain.|Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, 48170, Zamudio, Spain.
authors.forename: Izaskun
authors.initials: I
authors.lastname: Elezgarai
authors.affiliation: Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom.|Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128, Mainz, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ruehle
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128, Mainz, Germany.
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.affiliation: Department of Neurosciences, University of the Basque Country UPV/EHU, E-48940, Leioa, Spain.|Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, 48170, Zamudio, Spain.
authors.forename: Leire
authors.initials: L
authors.lastname: Reguero
authors.affiliation: Department of Neurosciences, University of the Basque Country UPV/EHU, E-48940, Leioa, Spain.|Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, 48170, Zamudio, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Gerrikagoitia
authors.affiliation: Université de Bordeaux, Bordeaux, F-33076, France.|INSERM, U1215 Neurocentre Magendie, Endocannabinoids and Neuroadaptation, Bordeaux, 33077, France.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.affiliation: Department of Neurosciences, University of the Basque Country UPV/EHU, E-48940, Leioa, Spain.|Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, 48170, Zamudio, Spain.|Division of Medical Sciences, University of Victoria, Victoria, V8P 5C2, British Columbia, Canada.
authors.forename: Pedro
authors.initials: P
authors.lastname: Grandes
mesh_terms: D000818:Animals; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure*; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis*
chemical_list: D043884:Receptor, Cannabinoid, CB1
keywords: RRID:AB_2571530; electron microscopy; endocannabinoid system; hippocampus; knockin rodents; synapses