title: 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.
authors.affiliation: Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Sigmund-Freud Str. 25, 53105, Bonn, Germany.
authors.forename: Önder
authors.initials: Ö
authors.lastname: Albayram
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Sigmund-Freud Str. 25, 53105, Bonn, Germany.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Passlick
authors.affiliation: Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Sigmund-Freud Str. 25, 53105, Bonn, Germany.
authors.forename: Andras
authors.initials: A
authors.lastname: Bilkei-Gorzo
authors.affiliation: Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Sigmund-Freud Str. 25, 53105, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Sigmund-Freud Str. 25, 53105, Bonn, Germany. christian.steinhaeuser@ukb.uni-bonn.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Steinhäuser
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D003071:Cognition; D059330:GABAergic Neurons / Q000378:metabolism* / Q000502:physiology; D007395:Interneurons / Q000378:metabolism* / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning; D051379:Mice; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D043884:Receptor, Cannabinoid, CB1
keywords: CA1 pyramidal neurons; CB1 receptor knockout; Cannabinoid signaling; Field potential; Learning and memory