Neuron-type specific cannabinoid-mediated G protein signalling in mouse hippocampus.
Frauke Steindel,Raissa Lerner,Martin Häring,Sabine Ruehle,Giovanni Marsicano,Giovanni Marsicano,Beat Lutz,Krisztina Monory +7 more
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TLDR
It is confirmed that CB1 is present at much higher density on hippocampal GABAergic interneurons than glutamatergic neurons, and this selective signalling mechanism raises the possibility of designing novel cannabinoid ligands that differentially activate only a subset of physiological effects of CB1 stimulation, thereby optimizing therapeutic action.Abstract:
Type 1 cannabinoid receptor (CB1) is expressed in different neuronal populations in the mammalian brain. In particular, CB1 on GABAergic or glutamatergic neurons exerts different functions and display different pharmacological properties in vivo. This suggests the existence of neuron-type specific signalling pathways activated by different subpopulations of CB1. In this study, we analysed CB1 expression, binding and signalling in the hippocampus of conditional mutant mice, bearing CB1 deletion in GABAergic (GABA-CB1-KO mice) or cortical glutamatergic neurons (Glu-CB1-KO mice). Compared to their wild-type littermates, Glu-CB1-KO displayed a small decrease of CB1 mRNA amount, immunoreactivity and [³H]CP55,940 binding. Conversely, GABA-CB1-KO mice showed a drastic reduction of these parameters, confirming that CB1 is present at much higher density on hippocampal GABAergic interneurons than glutamatergic neurons. Surprisingly, however, saturation analysis of HU210-stimulated [(35) S]GTPγS binding demonstrated that 'glutamatergic' CB1 is more efficiently coupled to G protein signalling than 'GABAergic' CB1. Thus, the minority of CB1 on glutamatergic neurons is paradoxically several fold more strongly coupled to G protein signalling than 'GABAergic' CB1. This selective signalling mechanism raises the possibility of designing novel cannabinoid ligands that differentially activate only a subset of physiological effects of CB1 stimulation, thereby optimizing therapeutic action.read more
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Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus
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TL;DR: The data indicate that cortical feedback projections to the MOB crucially regulate food intake via CB1 receptor signaling, linking the feeling of hunger to stronger odor processing.
References
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István Katona,Beáta Sperlágh,Attila Sik,Attila Käfalvi,E. Sylvester Vizi,Ken Mackie,Tamás F. Freund +6 more
TL;DR: The results suggest that cannabinoid-mediated modulation of hippocampal interneuron networks operate largely via presynaptic receptors on CCK-immunoreactive basket cell terminals, the likely mechanism by which both endogenous and exogenous CB1 ligands interfere with hippocampal network oscillations and associated cognitive functions.
Journal ArticleDOI
CB1 cannabinoid receptors and on-demand defense against excitotoxicity.
Giovanni Marsicano,Sharon Goodenough,Sharon Goodenough,Krisztina Monory,Heike Hermann,Matthias Eder,Astrid Cannich,Shahnaz Christina Azad,Maria Grazia Cascio,Silvia Ortega Gutierrez,Mario van der Stelt,María L. López-Rodríguez,Emilio Casanova,Günther Schütz,Walter Zieglgänsberger,Vincenzo Di Marzo,Christian Behl,Beat Lutz +17 more
TL;DR: The endogenous cannabinoid system provides on-demand protection against acute excitotoxicity in central nervous system neurons and could not be triggered in mutant mice.
Journal ArticleDOI
Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain
Giovanni Marsicano,Beat Lutz +1 more
TL;DR: It is suggested that a putative cross‐talk between cannabinoids and CCK might exist and will be relevant to better understanding of physiology and pharmacology of the cannabinoid system.
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