Endocannabinoid-mediated metaplasticity in the hippocampus.
Repetitive activation of glutamatergic fibers that normally induces long-term potentiation (LTP) at excitatory synapses in the hippocampus also triggers long-term depression at inhibitory synapses (I-LTD) via retrograde endocannabinoid signaling. Little is known, however, about the physiological significance of I-LTD. Here, we show that synaptic-driven release of endocannabinoids is a highly localized and efficient process that strongly depresses cannabinoid-sensitive inhibitory inputs within the dendritic compartment of CA1 pyramidal cells. By removing synaptic inhibition in a restricted area of the dendritic tree, endocannabinoids selectively "primed" nearby excitatory synapses, thereby facilitating subsequent induction of LTP. This induction of local metaplasticity is a novel mechanism by which endocannabinoids can contribute to the storage of information in the brain.
Chevaleyre
Vivien
V
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Castillo
Pablo E
PE
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology* / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D010852:Picrotoxin / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency; D013569:Synapses / Q000502:physiology / Q000528:radiation effects; D013997:Time Factors
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251