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Nat Neurosci. 2015 Jan;18(1):75-86. doi: 10.1038/nn.3892. Epub 2014 Dec 8.

Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling.

Author information

1
Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
2
School of Ph.D. Studies, Semmelweis University, Budapest, Hungar.
3
Department of Anatomy and Neurobiology, University of California, Irvine, USA.
4
Alfred Renyi Institute of Mathematics, Hungarian Academy of Sciences, Budapest, Hungary.
5
ImmunoGenes Kft, Budakeszi, Hungary.
6
Department of Immunology, Eötvös Loránd University Budapest, Hungary.
7
Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan.
8
Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Italy.
9
CNR Neuroscience Institute, Cagliari, Italy.
#
Contributed equally

Abstract

A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell type- and subcellular compartment-specific manner. We developed a new approach to this problem by combining cell-specific physiological and anatomical characterization with super-resolution imaging and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically projecting GABAergic interneurons possessed increased CB1 receptor number, active-zone complexity and receptor/effector ratio compared with dendritically projecting interneurons, consistent with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ(9)-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ(9)-tetrahydrocannabinol treatment. These findings indicate that cell type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits and identify previously unknown molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction.

PMID:
25485758
PMCID:
PMC4281300
DOI:
10.1038/nn.3892
[Indexed for MEDLINE]
Free PMC Article

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