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Anatomical characterization of the cannabinoid CB 1 receptor in cell‐type–specific mutant mouse rescue models
Author(s) -
GutiérrezRodríguez Ana,
Puente Nagore,
Elezgarai Izaskun,
Ruehle Sabine,
Lutz Beat,
Reguero Leire,
Gerrikagoitia Inmaculada,
Marsicano Giovanni,
Grandes Pedro
Publication year - 2017
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.24066
Subject(s) - glutamatergic , gabaergic , biology , neuroscience , inhibitory postsynaptic potential , receptor , hippocampal formation , excitatory postsynaptic potential , ampa receptor , microbiology and biotechnology , glutamate receptor , biochemistry
Type 1 cannabinoid (CB 1 ) 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 CB 1 receptors can be overlooked, fostering an incomplete mapping. To overcome this, knockin mice with cell‐type–specific rescue of CB 1 receptors have emerged as excellent tools for investigating CB 1 receptors’ cell‐type–specific localization and sufficient functional role with no bias. However, to know whether these rescue mice maintain endogenous CB 1 receptor expression level, detailed anatomical studies are necessary. The subcellular distribution of hippocampal CB 1 receptors of rescue mice that express the gene exclusively in dorsal telencephalic glutamatergic neurons (Glu‐ CB 1 ‐RS) or GABAergic neurons (GABA‐ CB 1 ‐RS) was studied by immunoelectron microscopy. Results were compared with conditional CB 1 receptor knockout lines. As expected, CB 1 immunoparticles appeared at presynaptic plasmalemma, making asymmetric and symmetric synapses. In the hippocampal CA1 stratum radiatum, the values of the CB 1 receptor‐immunopositive excitatory and inhibitory synapses were Glu‐ CB 1 ‐RS, 21.89% (glutamatergic terminals); 2.38% (GABAergic terminals); GABA‐ CB 1 ‐RS, 1.92% (glutamatergic terminals); 77.92% (GABAergic terminals). The proportion of CB 1 receptor‐immunopositive excitatory and inhibitory synapses in the inner one‐third of the dentate molecular layer was Glu‐ CB 1 ‐RS, 53.19% (glutamatergic terminals); 2.30% (GABAergic terminals); GABA‐ CB 1 ‐RS, 3.19% (glutamatergic terminals); 85.07% (GABAergic terminals). Taken together, Glu‐ CB 1 ‐RS and GABA‐ CB 1 ‐RS mice show the usual CB 1 receptor 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.