Abstract
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.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cannabinoid Receptor Modulators / physiology*
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Dose-Response Relationship, Radiation
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Electric Stimulation / methods
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Endocannabinoids*
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / radiation effects
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GABA Antagonists / pharmacology
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Hippocampus / cytology
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Hippocampus / physiology*
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Hippocampus / radiation effects
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In Vitro Techniques
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Long-Term Synaptic Depression / physiology
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Long-Term Synaptic Depression / radiation effects
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neural Inhibition / physiology*
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Neural Inhibition / radiation effects
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Neuronal Plasticity / physiology*
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Neuronal Plasticity / radiation effects
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Neurons / drug effects
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Neurons / physiology
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Neurons / radiation effects
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Picrotoxin / pharmacology
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Piperidines / pharmacology
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Pyrazoles / pharmacology
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Receptor, Cannabinoid, CB1 / deficiency
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Synapses / physiology
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Synapses / radiation effects
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Time Factors
Substances
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Cannabinoid Receptor Modulators
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Endocannabinoids
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Piperidines
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Pyrazoles
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Receptor, Cannabinoid, CB1
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Picrotoxin
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AM 251