Cannabinoids reveal importance of spike timing coordination in hippocampal function.
Cannabinoids impair hippocampus-dependent memory in both humans and animals, but the network mechanisms responsible for this effect are unknown. Here we show that the cannabinoids Delta(9)-tetrahydrocannabinol and CP55940 decreased the power of theta, gamma and ripple oscillations in the hippocampus of head-restrained and freely moving rats. These effects were blocked by a CB1 antagonist. The decrease in theta power correlated with memory impairment in a hippocampus-dependent task. By simultaneously recording from large populations of single units, we found that CP55940 severely disrupted the temporal coordination of cell assemblies in short time windows (<100 ms) yet only marginally affected population firing rates of pyramidal cells and interneurons. The decreased power of local field potential oscillations correlated with reduced temporal synchrony but not with firing rate changes. We hypothesize that reduced spike timing coordination and the associated impairment of physiological oscillations are responsible for cannabinoid-induced memory deficits.
Robbe
David
D
Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, USA.
Montgomery
Sean M
SM
Thome
Alexander
A
Rueda-Orozco
Pavel E
PE
McNaughton
Bruce L
BL
Buzsaki
György
G
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D003344:Cortical Synchronization / Q000187:drug effects; D003510:Cyclohexanes / Q000494:pharmacology; D003511:Cyclohexanols; D013759:Dronabinol / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010507:Periodicity; D010636:Phenols / Q000494:pharmacology; D051381:Rats; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000502:physiology; D013826:Theta Rhythm / Q000187:drug effects*
D002186:Cannabinoids; D003510:Cyclohexanes; D003511:Cyclohexanols; D010636:Phenols; D043882:Receptors, Cannabinoid; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol