title: State-dependent, bidirectional modulation of neural network activity by endocannabinoids.
abstract: The endocannabinoid (eCB) system and the cannabinoid CB1 receptor (CB1R) play key roles in the modulation of brain functions. Although actions of eCBs and CB1Rs are well described at the synaptic level, little is known of their modulation of neural activity at the network level. Using microelectrode arrays, we have examined the role of CB1R activation in the modulation of the electrical activity of rat and mice cortical neural networks in vitro. We find that exogenous activation of CB1Rs expressed on glutamatergic neurons decreases the spontaneous activity of cortical neural networks. Moreover, we observe that the net effect of the CB1R antagonist AM251 inversely correlates with the initial level of activity in the network: blocking CB1Rs increases network activity when basal network activity is low, whereas it depresses spontaneous activity when its initial level is high. Our results reveal a complex role of CB1Rs in shaping spontaneous network activity, and suggest that the outcome of endogenous neuromodulation on network function might be state dependent.
authors.affiliation: Neurocentre Magendie INSERM U862, 33077 Bordeaux Cedex, France. richard.piet@otago.ac.nz
authors.forename: Richard
authors.initials: R
authors.lastname: Piet
authors.forename: André
authors.initials: A
authors.lastname: Garenne
authors.forename: Fanny
authors.initials: F
authors.lastname: Farrugia
authors.forename: Gwendal
authors.initials: G
authors.lastname: Le Masson
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Pascale
authors.initials: P
authors.lastname: Chavis
authors.forename: Olivier J
authors.initials: OJ
authors.lastname: Manzoni
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001581:Benzothiadiazines / Q000494:pharmacology; D001921:Brain / Q000166:cytology*; D063385:Cannabinoid Receptor Modulators / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D015761:4-Aminopyridine; D001581:Benzothiadiazines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D010880:Piperidines; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D011810:Quinoxalines; D043884:Receptor, Cannabinoid, CB1; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D014633:Valine; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C107353:CGP 54626; C103505:AM 251; C056639:2-amino-5-phosphopentanoic acid; C004639:cyclothiazide
references.citation: Nat Neurosci. 2009 Dec;12(12):1488-90
references.pmid: 19915567
references.citation: J Neurosci. 2006 Feb 1;26(5):1465-9
references.pmid: 16452670
references.citation: Science. 2007 May 25;316(5828):1212-6
references.pmid: 17525344
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8760-5
references.pmid: 18562289
references.citation: Brain Res Brain Res Rev. 2000 Mar;31(2-3):295-301
references.pmid: 10719156
references.citation: PLoS Biol. 2010 Apr 06;8(4):e1000348
references.pmid: 20386723
references.citation: J Virol. 2007 Aug;81(16):8833-7
references.pmid: 17553893
references.citation: Nat Neurosci. 2010 Mar;13(3):281-3
references.pmid: 20139974
references.citation: J Neurosci Methods. 2005 Jun 30;145(1-2):23-35
references.pmid: 15922023
references.citation: Neuron. 1998 Jan;20(1):135-41
references.pmid: 9459449
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1362-7
references.pmid: 14734812
references.citation: Neuron. 2002 May 30;34(5):787-96
references.pmid: 12062024
references.citation: Nat Med. 2008 Sep;14(9):923-30
references.pmid: 18776886
references.citation: Prog Neurobiol. 1992 Oct;39(4):337-88
references.pmid: 1354387
references.citation: Physiol Rev. 2009 Jan;89(1):309-80
references.pmid: 19126760
references.citation: Annu Rev Physiol. 2009;71:283-306
references.pmid: 19575681
references.citation: J Neurosci. 2006 Aug 2;26(31):8148-59
references.pmid: 16885228
references.citation: J Neurosci. 2007 Sep 19;27(38):10165-75
references.pmid: 17881522
references.citation: Nature. 2004 Sep 16;431(7006):312-6
references.pmid: 15372034
references.citation: J Neurosci Methods. 2008 Aug 30;173(2):183-92
references.pmid: 18590768
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2939-44
references.pmid: 19196976
references.citation: J Neurosci. 2005 Jun 29;25(26):6127-36
references.pmid: 15987942
references.citation: Neuron. 2006 Aug 17;51(4):455-66
references.pmid: 16908411
references.citation: Nat Neurosci. 1998 Jul;1(3):201-9
references.pmid: 10195144
references.citation: J Neurosci. 2007 Feb 7;27(6):1325-33
references.pmid: 17287507
references.citation: Life Sci. 2005 Feb 4;76(12):1307-24
references.pmid: 15670612
references.citation: Comput Intell Neurosci. 2007;:12725
references.pmid: 18350128
references.citation: Trends Neurosci. 1998 Dec;21(12):521-8
references.pmid: 9881850