Cannabinoids disrupt hippocampal sharp wave-ripples via inhibition of glutamate release

Nikolaus Maier, Genela Morris, Sebastian Schuchmann, Tatiana Korotkova, Alexey Ponomarenko, Claudia Böhm, Christian Wozny, Dietmar Schmitz

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Cannabis consumption results in impaired learning. The proper synchronization of neuronal activity in the mammalian hippocampus gives rise to network rhythms that are implicated in memory formation. Here, we have studied the impact of cannabinoids on hippocampal sharp waves and associated ripple oscillations using field- and whole-cell voltage-clamp recordings. We demonstrate that the activation of cannabinoid receptor 1 suppresses sharp wave-ripples (SWRs) in mice in vivo and in vitro. This suppression was paralleled by a selective reduction of SWR-associated inward but not outward charge transfer, demonstrating an impairment of excitation due to cannabinoid exposure. Adenosine, a presynaptic modulator of glutamate release, mimicked and occluded the observed consequences of cannabinoids on SWRs. We conclude that inhibition of glutamatergic feed-forward excitation can explain cannabinoid-mediated disruption of SWRs and may account for cannabinoid-induced impairment of hippocampus-dependent memory.

Original languageEnglish
Pages (from-to)1350-62
Number of pages13
JournalHippocampus
Volume22
Issue number6
DOIs
Publication statusPublished - 30 Jun 2012

Keywords

  • animals
  • cannabinoids
  • cyclohexanols
  • dose-response relationship, Drug
  • female
  • glutamic acid
  • hippocampus
  • male
  • mice
  • mice, inbred C57BL
  • nerve net
  • neural inhibition
  • receptor, cannabinoid, CB1

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    Maier, N., Morris, G., Schuchmann, S., Korotkova, T., Ponomarenko, A., Böhm, C., ... Schmitz, D. (2012). Cannabinoids disrupt hippocampal sharp wave-ripples via inhibition of glutamate release. Hippocampus, 22(6), 1350-62. https://doi.org/10.1002/hipo.20971