title: Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus.
abstract: Endocannabinoids (eCBs) exert major control over neuronal activity by activating cannabinoid receptors (CBRs). The functionality of the eCB system is primarily ascribed to the well-documented retrograde activation of presynaptic CB1Rs. We find that action potential-driven eCB release leads to a long-lasting membrane potential hyperpolarization in hippocampal principal cells that is independent of CB1Rs. The hyperpolarization, which is specific to CA3 and CA2 pyramidal cells (PCs), depends on the activation of neuronal CB2Rs, as shown by a combined pharmacogenetic and immunohistochemical approach. Upon activation, they modulate the activity of the sodium-bicarbonate co-transporter, leading to a hyperpolarization of the neuron. CB2R activation occurred in a purely self-regulatory manner, robustly altered the input/output function of CA3 PCs, and modulated gamma oscillations in vivo. To conclude, we describe a cell type-specific plasticity mechanism in the hippocampus that provides evidence for the neuronal expression of CB2Rs and emphasizes their importance in basic neuronal transmission.
authors.affiliation: Neuroscience Research Center (NWFZ), 10117 Berlin, Germany. Electronic address: vstempel@mrc-lmb.cam.ac.uk.
authors.forename: A Vanessa
authors.initials: AV
authors.lastname: Stempel
authors.affiliation: Neuroscience Research Center (NWFZ), 10117 Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stumpf
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Neuroscience Research Center (NWFZ), 10117 Berlin, Germany.
authors.forename: Tuğba
authors.initials: T
authors.lastname: Özdoğan
authors.affiliation: Neuroscience Research Center (NWFZ), 10117 Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pannasch
authors.affiliation: Neuroscience Research Center (NWFZ), 10117 Berlin, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Theis
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany.
authors.forename: David-Marian
authors.initials: DM
authors.lastname: Otte
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wojtalla
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Rácz
authors.affiliation: NeuroCure Cluster of Excellence, 10117 Berlin, Germany; Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.
authors.forename: Alexey
authors.initials: A
authors.lastname: Ponomarenko
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Zheng-Xiong
authors.initials: ZX
authors.lastname: Xi
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Neuroscience Research Center (NWFZ), 10117 Berlin, Germany; NeuroCure Cluster of Excellence, 10117 Berlin, Germany; Bernstein Center for Computational Neuroscience (BCCN), 10115 Berlin, Germany; Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany; Einstein Center for Neurosciences, 10117 Berlin, Germany. Electronic address: dietmar.schmitz@charite.de.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043885:Receptor, Cannabinoid, CB2; D018094:Receptors, Metabotropic Glutamate