Physiological impact of CB1 receptor expression by hippocampal GABAergic interneurons
Abstract
A subset of hippocampal GABAergic neurons, which are cholecystokinin-positive, highly express cannabinoid type 1 (CB1) receptors. Activation of these receptors inhibits GABA release and thereby limits inhibitory control. While genetic deletion of CB1 receptors from GABAergic neurons led to behavioural alterations and neuroinflammatory reactions, it remained unclear whether these changes in the knockout animals were a direct consequence of the enhanced transmitter release or reflected developmental deficits. The hippocampus is vital for the generation of spatial, declarative and working memory. Here, we addressed the question how CB1 receptors in GABAergic neurons influence hippocampal function. Patch clamp and field potential recordings in mice devoid of CB1 receptors in GABAergic neurons revealed an enhanced frequency and faster kinetics of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons while tonic inhibition, paired-pulse facilitation and long-term potentiation in the hippocampus were not affected. Evaluation of cognitive functions demonstrated impaired acquisition of spatial memory and deficits in novel object recognition and partner recognition in the knockout mice, while working memory and spatial memory remained intact. The density of GABAergic neurons was also similar in knockout mice and their littermates, which argues against global deficits in hippocampal development. Together, these results suggest that CB1 receptors in GABAergic neurons influence specific aspects of neuronal excitability and hippocampal learning.
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Mice with selective knockout of cannabinoid 1-R in GABAergic neurons exhibited disruption of NOP (30 min) memory and facilitation of spontaneous IPSC in CA1 pyramidal neurons in vitro.
“Mice with selective knockout of cannabinoid 1-R in the GABAergic neurons, exhibited disruption of NOP (30 min) memory, and facilitation of spontaneous IPSC in the CA1 pyramidal neurons in vitro”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Albayram et al., 2016
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Hippocampal GABAergic Inhibitory Interneurons
Pelkey, K. A., Chittajallu, R., Craig, M. T., Tricoire, L., Wester, J. C., & McBain, C. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00007.2017 · Cited by 889 · see citing works
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- Authors
- Albayram, Ö., Passlick, S., Bilkei-Gorzo, A., Zimmer, A., & Steinhäuser, C.
- Affiliations
- University of Bonn (DE)
- Corresponding author
- Steinhäuser, Christian
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2016-01-07
- Volume
- 468
- Issue
- 4
- Pages
- 727-737
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- OpenAlex
- W2224409683
- Cited by
- 42
- References
- 58
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 11 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 5 · 2016: 3 · 2014: 1
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (STE552/3, FOR926 SP2, BI-1227/5-1, FOR926 CP2)
- Seventh Framework Programme (ESF EuroEPINOMICS)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- CB1 receptor, cholecystokinin, CB1 knockout mice, CA1 pyramidal neurons, inhibitory postsynaptic currents, tonic inhibition, paired-pulse facilitation, long-term potentiation, spatial memory, novel object recognition, partner identification, working memory, neuronal excitability, hippocampal development
- MeSH terms
- Animals, Cognition, Interneurons, Male, Long-Term Potentiation, Maze Learning, Receptor, Cannabinoid, CB1, Mice, CA1 Region, Hippocampal, GABAergic Neurons
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