title: Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling.
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.
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.|School of Ph.D. Studies, Semmelweis University, Budapest, Hungar.
authors.forename: Barna
authors.initials: B
authors.lastname: Dudok
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Barna
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Marco
authors.initials: M
authors.lastname: Ledri
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Szilárd I
authors.initials: SI
authors.lastname: Szabó
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Szabadits
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Pintér
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Woodhams
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Henstridge
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.|School of Ph.D. Studies, Semmelweis University, Budapest, Hungar.
authors.forename: Gyula Y
authors.initials: GY
authors.lastname: Balla
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Nyilas
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, USA.
authors.forename: Csaba
authors.initials: C
authors.lastname: Varga
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, USA.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Alfred Renyi Institute of Mathematics, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Máté
authors.initials: M
authors.lastname: Matolcsi
authors.affiliation: ImmunoGenes Kft, Budakeszi, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Cervenak
authors.affiliation: ImmunoGenes Kft, Budakeszi, Hungary.|Department of Immunology, Eötvös Loránd University Budapest, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Kacskovics
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sagheddu
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Melis
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Italy.|CNR Neuroscience Institute, Cagliari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pistis
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Soltesz
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Katona
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006624:Hippocampus / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007395:Interneurons / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059906:Neuroimaging / Q000379:methods*; D017729:Presynaptic Terminals / Q000502:physiology / Q000648:ultrastructure; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D043882:Receptors, Cannabinoid / Q000502:physiology* / Q000648:ultrastructure*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D043882:Receptors, Cannabinoid; D005680:gamma-Aminobutyric Acid