GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus

I. Katona, B. Sperlágh, Z. Maglóczky, E. Sántha, A. Köfalvi, S. Czirják, K. Mackie, E. Vízi, T. Freund

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Cannabinoids have been shown to disrupt memory processes in mammals including humans. Although the CB1 neuronal cannabinoid receptor was identified several years ago, neuronal network mechanisms mediating cannabinoid effects are still controversial in animals, and even more obscure in humans. In the present study, the localization of CB1 receptors was investigated at the cellular and subcellular levels in the human hippocampus, using control post mortem and epileptic lobectomy tissue. The latter tissue was also used for [3H]GABA release experiments, testing the predictions of the anatomical data. Detectable expression of CB1 was confined to interneurons, most of which were found to be cholecystokinin-containing basket cells. CB1-positive cell bodies showed immunostaining in their perinuclear cytoplasm, but not in their somadendritic plasmamembrane. CB1-immunoreactive axon terminals densely covered the entire hippocampus, forming symmetrical synapses characteristic of GABAergic boutons. Human temporal lobectomy samples were used in the release experiments, as they were similar to the controls regarding cellular and subcellular distribution of CB1 receptors. We found that the CB1 receptor agonist, WIN 55,212-2, strongly reduced [3H]GABA release, and this effect was fully prevented by the specific CB1 receptor antagonist SR 141716A.This unique expression pattern and the presynaptic modulation of GABA release suggests a conserved role for CB1 receptors in controlling inhibitory networks of the hippocampus that are responsible for the generation and maintenance of fast and slow oscillatory patterns. Therefore, a likely mechanism by which cannabinoids may impair memory and associational processes is an alteration of the fine-tuning of synchronized, rhythmic population events. Copyright (C) 2000 IBRO.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalNeuroscience
Volume100
Issue number4
DOIs
Publication statusPublished - Oct 11 2000

Fingerprint

Cannabinoid Receptor CB1
Cannabinoids
Interneurons
Hippocampus
rimonabant
gamma-Aminobutyric Acid
GABA Agents
Cholecystokinin
Presynaptic Terminals
Synapses
Mammals
Cytoplasm
Maintenance
Population

Keywords

  • CB1 receptor
  • Cholecystokinin
  • Memory
  • Presynaptic
  • Release
  • Synchronization

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus. / Katona, I.; Sperlágh, B.; Maglóczky, Z.; Sántha, E.; Köfalvi, A.; Czirják, S.; Mackie, K.; Vízi, E.; Freund, T.

In: Neuroscience, Vol. 100, No. 4, 11.10.2000, p. 797-804.

Research output: Contribution to journalArticle

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AU - Katona, I.

AU - Sperlágh, B.

AU - Maglóczky, Z.

AU - Sántha, E.

AU - Köfalvi, A.

AU - Czirják, S.

AU - Mackie, K.

AU - Vízi, E.

AU - Freund, T.

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N2 - Cannabinoids have been shown to disrupt memory processes in mammals including humans. Although the CB1 neuronal cannabinoid receptor was identified several years ago, neuronal network mechanisms mediating cannabinoid effects are still controversial in animals, and even more obscure in humans. In the present study, the localization of CB1 receptors was investigated at the cellular and subcellular levels in the human hippocampus, using control post mortem and epileptic lobectomy tissue. The latter tissue was also used for [3H]GABA release experiments, testing the predictions of the anatomical data. Detectable expression of CB1 was confined to interneurons, most of which were found to be cholecystokinin-containing basket cells. CB1-positive cell bodies showed immunostaining in their perinuclear cytoplasm, but not in their somadendritic plasmamembrane. CB1-immunoreactive axon terminals densely covered the entire hippocampus, forming symmetrical synapses characteristic of GABAergic boutons. Human temporal lobectomy samples were used in the release experiments, as they were similar to the controls regarding cellular and subcellular distribution of CB1 receptors. We found that the CB1 receptor agonist, WIN 55,212-2, strongly reduced [3H]GABA release, and this effect was fully prevented by the specific CB1 receptor antagonist SR 141716A.This unique expression pattern and the presynaptic modulation of GABA release suggests a conserved role for CB1 receptors in controlling inhibitory networks of the hippocampus that are responsible for the generation and maintenance of fast and slow oscillatory patterns. Therefore, a likely mechanism by which cannabinoids may impair memory and associational processes is an alteration of the fine-tuning of synchronized, rhythmic population events. Copyright (C) 2000 IBRO.

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