State-dependent, bidirectional modulation of neural network activity by endocannabinoids

• Published in: The Journal of neuroscience Vol. 31; no. 46; pp. 16591 - 16596
• Main Authors: Piet, Richard, Garenne, André, Farrugia, Fanny, Le Masson, Gwendal, Marsicano, Giovanni, Chavis, Pascale, Manzoni, Olivier J
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 16-11-2011
• Subjects: 4-Aminopyridine - pharmacology; Action Potentials - drug effects; Action Potentials - genetics; Animals; Animals, Newborn; Benzothiadiazines - pharmacology; Brain - cytology; Brief Communications; Cannabinoid Receptor Modulators - agonists; Cannabinoid Receptor Modulators - antagonists & inhibitors; Cannabinoid Receptor Modulators - metabolism; Cells, Cultured; Electric Stimulation; Endocannabinoids; Excitatory Amino Acid Antagonists - pharmacology; GABA Antagonists; In Vitro Techniques; Mice; Mice, Transgenic; Nerve Net - drug effects; Nerve Net - physiology; Neural Inhibition - drug effects; Neural Inhibition - genetics; Neurons - classification; Neurons - drug effects; Neurons - physiology; Organophosphorus Compounds - pharmacology; Picrotoxin - pharmacology; Piperidines - pharmacology; Potassium Channel Blockers - pharmacology; Pyrazoles - pharmacology; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - deficiency; Sodium Channel Blockers - pharmacology; Tetrodotoxin - pharmacology; Valine - analogs & derivatives; Valine - pharmacology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.4297-11.2011

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.