Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony.
Proceedings of the National Academy of Sciences. 2012-12-26; 110(2): 719-724
DOI: 10.1073/pnas.1217144110
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1. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):719-24. doi: 10.1073/pnas.1217144110.
Epub 2012 Dec 26.
Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects
of cannabinoids on cortical network synchrony.
Sales-Carbonell C(1), Rueda-Orozco PE, Soria-Gómez E, Buzsáki G, Marsicano G,
Robbe D.
Author information:
(1)Department of Systems Neuroscience, Institut d’Investigacions Biomèdiques
August Pi i Sunyer, 08016 Barcelona, Spain.
Activation of type 1 cannabinoid receptors (CB1R) decreases GABA and glutamate
release in cortical and subcortical regions, with complex outcomes on cortical
network activity. To date there have been few attempts to disentangle the region-
and cell-specific mechanisms underlying the effects of cannabinoids on cortical
network activity in vivo. Here we addressed this issue by combining in vivo
electrophysiological recordings with local and systemic pharmacological
manipulations in conditional mutant mice lacking CB1R expression in different
neuronal populations. First we report that cannabinoids induce hypersynchronous
thalamocortical oscillations while decreasing the amplitude of faster cortical
oscillations. Then we demonstrate that CB1R at striatonigral synapses (basal
ganglia direct pathway) mediate the thalamocortical hypersynchrony, whereas
activation of CB1R expressed in cortical glutamatergic neurons decreases cortical
synchrony. Finally we show that activation of CB1 expressed in cortical
glutamatergic neurons limits the cannabinoid-induced thalamocortical
hypersynchrony. By reporting that CB1R activations in cortical and subcortical
regions have contrasting effects on cortical synchrony, our study bridges the gap
between cellular and in vivo network effects of cannabinoids. Incidentally, the
thalamocortical hypersynchrony we report suggests a potential mechanism to
explain the sensory “high” experienced during recreational consumption of
marijuana.
DOI: 10.1073/pnas.1217144110
PMCID: PMC3545808
PMID: 23269835 [Indexed for MEDLINE]