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

Barna Dudok; László Barna; Marco Ledri; Szilárd I. Szabó; Eszter Szabadits; Balázs Pintér; Stephen G. Woodhams; Christopher M. Henstridge; Gyula Y. Balla; Rita Nyilas; Csaba Varga; Sang Hun Lee; Máté Matolcsi; Judit Cervenak; Imre Kacskovics; Masahiko Watanabe; Claudia Sagheddu; Miriam Melis; Marco Pistis; Ivan Soltesz; István Katona

doi:10.1038/nn.3892

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

Barna Dudok, László Barna, Marco Ledri, Szilárd I. Szabó, Eszter Szabadits, Balázs Pintér, Stephen G. Woodhams, Christopher M. Henstridge, Gyula Y. Balla, Rita Nyilas, Csaba Varga, Sang Hun Lee, Máté Matolcsi, Judit Cervenak, Imre Kacskovics, Masahiko Watanabe, Claudia Sagheddu, Miriam Melis, Marco Pistis, Ivan SolteszIstván Katona

Neuroscience

Research output: Contribution to journal › Article › peer-review

194 Scopus citations

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 CB 1 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 Δ⁹-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB 1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ⁹-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.

Original language	English
Pages (from-to)	75-86
Number of pages	12
Journal	Nature Neuroscience
Volume	18
Issue number	1
DOIs	https://doi.org/10.1038/nn.3892
State	Published - Jan 1 2015

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© 2015 Nature America, Inc. All rights reserved.

ASJC Scopus subject areas

General Neuroscience

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Dudok, B., Barna, L., Ledri, M., Szabó, S. I., Szabadits, E., Pintér, B., Woodhams, S. G., Henstridge, C. M., Balla, G. Y., Nyilas, R., Varga, C., Lee, S. H., Matolcsi, M., Cervenak, J., Kacskovics, I., Watanabe, M., Sagheddu, C., Melis, M., Pistis, M., ... Katona, I. (2015). Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling. Nature Neuroscience, 18(1), 75-86. https://doi.org/10.1038/nn.3892

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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 CB 1 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 Δ9-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB 1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ9-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.",

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Dudok, B, Barna, L, Ledri, M, Szabó, SI, Szabadits, E, Pintér, B, Woodhams, SG, Henstridge, CM, Balla, GY, Nyilas, R, Varga, C, Lee, SH, Matolcsi, M, Cervenak, J, Kacskovics, I, Watanabe, M, Sagheddu, C, Melis, M, Pistis, M, Soltesz, I & Katona, I 2015, 'Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling', Nature Neuroscience, vol. 18, no. 1, pp. 75-86. https://doi.org/10.1038/nn.3892

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AU - Ledri, Marco

AU - Szabó, Szilárd I.

AU - Szabadits, Eszter

AU - Pintér, Balázs

AU - Woodhams, Stephen G.

AU - Henstridge, Christopher M.

AU - Balla, Gyula Y.

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AU - Varga, Csaba

AU - Lee, Sang Hun

AU - Matolcsi, Máté

AU - Cervenak, Judit

AU - Kacskovics, Imre

AU - Watanabe, Masahiko

AU - Sagheddu, Claudia

AU - Melis, Miriam

AU - Pistis, Marco

AU - Soltesz, Ivan

AU - Katona, István

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AB - 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 CB 1 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 Δ9-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB 1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ9-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.

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

Abstract

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