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, 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
N1 - Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
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
C2 - 25485758
AN - SCOPUS:84926213695
SN - 1097-6256
VL - 18
SP - 75
EP - 86
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 1
ER -