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Physiological impact of CB1 receptor expression by hippocampal GABAergic interneurons

  • Önder Albayram
  • Stefan Passlick
  • Andras Bilkei-Gorzo
  • Andreas Zimmer
  • Christian Steinhäuser
Neuroscience

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.

Keywords

CA1 pyramidal neurons Field potential Learning and memory Cannabinoid signaling CB1 receptor knockout 

Notes

Acknowledgments

We thank Drs. C. Henneberger and S. Künzel for comments on the manuscript and technical support. Grant Sponsors: Deutsche Forschungsgemeinschaft; STE552/3 (to CS), FOR926 SP2, BI-1227/5-1 (to ABG) and FOR926 CP2 (to AZ). European Union; ESF EuroEPINOMICS (to CS). A.Z. is a member of the DFG Cluster of Excellence ImmunoSensation.

Supplementary material

424_2015_1782_Fig6_ESM.jpg (200 kb)
ESM Fig. 1

Representative microphotographs of GAD67 immunostaining (green) in the CA1 and CA3 regions of the hippocampus of GABA/CB1+/+ and GABA/CB1-/- mice. White arrows indicate the location of GAD67+ cell bodies. Scale bar represents 100 μm (JPG 200 kb)

424_2015_1782_Fig7_ESM.jpg (235 kb)
ESM Fig. 2

Representative microphotographs of PV immunostaining (green) and Hoechst fluorescence (blue) in the CA1 and CA3 regions of the hippocampus of GABA/CB1+/+ and GABA/CB1-/- mice. White arrows indicate the location of PV+ interneurons. Scale bar represents 100 μm (JPG 235 kb)

424_2015_1782_Fig8_ESM.jpg (135 kb)
ESM Fig. 3

Representative microphotographs of CCK immunostaining (green) and Hoechst fluorescence (blue) in the CA1 and CA3 regions of the hippocampus of GABA/CB1+/+ and GABA/CB1-/- mice. White arrows indicate the location of CCK+ interneurons. Scale bar represents 100 μm (JPG 135 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Önder Albayram
    • 1
  • Stefan Passlick
    • 2
    • 3
  • Andras Bilkei-Gorzo
    • 1
  • Andreas Zimmer
    • 1
  • Christian Steinhäuser
    • 2
  1. 1.Institute of Molecular Psychiatry, Medical FacultyUniversity of BonnBonnGermany
  2. 2.Institute of Cellular Neurosciences, Medical FacultyUniversity of BonnBonnGermany
  3. 3.Department of NeuroscienceIcahn School of Medicine at Mount SinaiNew YorkUSA

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