Anatomical characterization of the cannabinoid CB1 receptor in cell-type-specific mutant mouse rescue models.

Ana Gutiérrez-Rodríguez, Nagore Puente, Izaskun Elezgarai, Sabine Ruehle, Beat Lutz, Leire Reguero, Inmaculada Gerrikagoitia, Giovanni Marsicano, Pedro Grandes
J. Comp. Neurol.. 2016-07-08; 525(2): 302-318
DOI: 10.1002/cne.24066

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1. J Comp Neurol. 2017 Feb 1;525(2):302-318. doi: 10.1002/cne.24066. Epub 2016 Jul

Anatomical characterization of the cannabinoid CB1 receptor in cell-type-specific
mutant mouse rescue models.

Gutiérrez-Rodríguez A(1)(2)(3), Puente N(1)(2), Elezgarai I(1)(2), Ruehle
S(4)(5), Lutz B(5), Reguero L(1)(2), Gerrikagoitia I(1)(2), Marsicano G(3)(6),
Grandes P(1)(2)(7).

Author information:
(1)Department of Neurosciences, University of the Basque Country UPV/EHU,
E-48940, Leioa, Spain.
(2)Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park,
48170, Zamudio, Spain.
(3)Université de Bordeaux, Bordeaux, F-33076, France.
(4)Division of Neurobiology, Medical Research Council Laboratory of Molecular
Biology, Cambridge, CB2 0QH, United Kingdom.
(5)Institute of Physiological Chemistry, University Medical Center of the
Johannes Gutenberg University Mainz, 55128, Mainz, Germany.
(6)INSERM, U1215 Neurocentre Magendie, Endocannabinoids and Neuroadaptation,
Bordeaux, 33077, France.
(7)Division of Medical Sciences, University of Victoria, Victoria, V8P 5C2,
British Columbia, Canada.

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 CB1 receptors can be overlooked, fostering an incomplete
mapping. To overcome this, knockin mice with cell-type-specific rescue of CB1
receptors have emerged as excellent tools for investigating CB1 receptors’
cell-type-specific localization and sufficient functional role with no bias.
However, to know whether these rescue mice maintain endogenous CB1 receptor
expression level, detailed anatomical studies are necessary. The subcellular
distribution of hippocampal CB1 receptors 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 CB1 receptor knockout lines. As expected,
CB1 immunoparticles appeared at presynaptic plasmalemma, making asymmetric and
symmetric synapses. In the hippocampal CA1 stratum radiatum, the values of the
CB1 receptor-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
CB1 receptor-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 CB1 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.

© 2016 Wiley Periodicals, Inc.

DOI: 10.1002/cne.24066
PMID: 27339436 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus