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, C. Varga, Sang Hun Lee, M. Matolcsi, Judit Cervenak, I. Kacskovics, Masahiko Watanabe, Claudia Sagheddu, Miriam Melis, Marco Pistis, Ivan Soltesz & 1 others I. Katona

Research output: Contribution to journalArticle

97 Citations (Scopus)

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 languageEnglish
Pages (from-to)75-86
Number of pages12
JournalNature Neuroscience
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Cannabinoids
Endocannabinoids
Dronabinol
Interneurons
Molecular Imaging
Presynaptic Terminals
Cannabis
Neurosciences
Synapses
gamma-Aminobutyric Acid
Hippocampus
Down-Regulation
Brain
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling. / Dudok, Barna; Barna, László; Ledri, Marco; Szabó, Szilárd I.; Szabadits, Eszter; Pintér, Balázs; Woodhams, Stephen G.; Henstridge, Christopher M.; Balla, Gyula Y.; Nyilas, Rita; Varga, C.; Lee, Sang Hun; Matolcsi, M.; Cervenak, Judit; Kacskovics, I.; Watanabe, Masahiko; Sagheddu, Claudia; Melis, Miriam; Pistis, Marco; Soltesz, Ivan; Katona, I.

In: Nature Neuroscience, Vol. 18, No. 1, 01.01.2015, p. 75-86.

Research output: Contribution to journalArticle

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
Dudok, Barna ; Barna, László ; Ledri, Marco ; Szabó, Szilárd I. ; Szabadits, Eszter ; Pintér, Balázs ; Woodhams, Stephen G. ; Henstridge, Christopher M. ; Balla, Gyula Y. ; Nyilas, Rita ; Varga, C. ; Lee, Sang Hun ; Matolcsi, M. ; Cervenak, Judit ; Kacskovics, I. ; Watanabe, Masahiko ; Sagheddu, Claudia ; Melis, Miriam ; Pistis, Marco ; Soltesz, Ivan ; Katona, I. / Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling. In: Nature Neuroscience. 2015 ; Vol. 18, No. 1. pp. 75-86.
@article{21c2048730f246349157177fe1ee87f7,
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.",
author = "Barna Dudok and L{\'a}szl{\'o} Barna and Marco Ledri and Szab{\'o}, {Szil{\'a}rd I.} and Eszter Szabadits and Bal{\'a}zs Pint{\'e}r and Woodhams, {Stephen G.} and Henstridge, {Christopher M.} and Balla, {Gyula Y.} and Rita Nyilas and C. Varga and Lee, {Sang Hun} and M. Matolcsi and Judit Cervenak and I. Kacskovics and Masahiko Watanabe and Claudia Sagheddu and Miriam Melis and Marco Pistis and Ivan Soltesz and I. Katona",
year = "2015",
month = "1",
day = "1",
doi = "10.1038/nn.3892",
language = "English",
volume = "18",
pages = "75--86",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling

AU - Dudok, Barna

AU - Barna, László

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.

AU - Nyilas, Rita

AU - Varga, C.

AU - Lee, Sang Hun

AU - Matolcsi, M.

AU - Cervenak, Judit

AU - Kacskovics, I.

AU - Watanabe, Masahiko

AU - Sagheddu, Claudia

AU - Melis, Miriam

AU - Pistis, Marco

AU - Soltesz, Ivan

AU - Katona, I.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84926213695&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926213695&partnerID=8YFLogxK

U2 - 10.1038/nn.3892

DO - 10.1038/nn.3892

M3 - Article

VL - 18

SP - 75

EP - 86

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 1

ER -