Neuron
Volume 90, Issue 4, 18 May 2016, Pages 795-809
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Article
Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus

https://doi.org/10.1016/j.neuron.2016.03.034Get rights and content
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Highlights

  • CB2Rs are expressed in hippocampal principal neurons

  • CB2Rs mediate a cell type-specific self-inhibitory plasticity in CA3/CA2 PCs

  • CB2Rs reduce the spike probability of CA3 PCs and alter gamma oscillations in vivo

  • CB2Rs act complementary to presynaptic CB1Rs

Summary

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.

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Present address: Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK