Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus

A. Vanessa Stempel, Alexander Stumpf, Hai Ying Zhang, Tuğba Özdoğan, Ulrike Pannasch, Anne Kathrin Theis, David Marian Otte, Alexandra Wojtalla, Ildikó Rácz, Alexey Ponomarenko, Zheng Xiong Xi, Andreas Zimmer, Dietmar Schmitz

Research output: Contribution to journalArticlepeer-review

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. The neuronal expression of CB2Rs has been a matter of long-standing debate. Stempel et al. demonstrate that CB2Rs are expressed in hippocampal principal cells and modulate neuronal function both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)795-809
Number of pages15
JournalNeuron
Volume90
Issue number4
DOIs
StatePublished - May 18 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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