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Cannabinoid type 2 receptors mediate a cell type-specific plasticity in the hippocampus

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Item Type:Article
Title:Cannabinoid type 2 receptors mediate a cell type-specific plasticity in the hippocampus
Creators Name:Stempel, A.V. and Stumpf, A. and Zhang, H.Y. and Özdoğan, T. and Pannasch, U. and Theis, A.K. and Otte, D.M. and Wojtalla, A. and Racz, I. and Ponomarenko, A. and Xi, Z.X. and Zimmer, A. and Schmitz, D.
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.
Keywords:Action Potentials, Cannabinoid CB2 Receptor, Cannabinoid Receptor Modulators, Endocannabinoids, Hippocampus, Long-Term Synaptic Depression, Metabotropic Glutamate Receptors, Neuronal Plasticity, Pyramidal Cells, Synapses, Synaptic Transmission, Animals, Mice
Source:Neuron
ISSN:0896-6273
Publisher:Cell Press / Elsevier
Volume:90
Number:4
Page Range:795-809
Date:18 May 2016
Official Publication:https://doi.org/10.1016/j.neuron.2016.03.034
PubMed:View item in PubMed

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