“Type-1 cannabinoid (CB1 ) receptors are widely distributed in the brain. Their physiological roles depend on their distribution pattern that differs remarkably among cell types. Hence, subcellular compartments with little but functional relevant CB1 receptors can be overlooked, fostering an incomplete mapping. To overcome this, knock-in mice with cell-type specific rescue of CB1 receptors have emerged as excellent tools to investigate its 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 called for. 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 knock-out lines.
As expected, CB1immunoparticles 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 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, being therefore ideal for in-depth anatomical and functional investigations of the endocannabinoid system.”