Abstract
Febrile (fever-induced) seizures are the most common form of childhood seizures, affecting 3%-5% of infants and young children. Here we show that the activity-dependent, retrograde inhibition of GABA release by endogenous cannabinoids is persistently enhanced in the rat hippocampus following a single episode of experimental prolonged febrile seizures during early postnatal development. The potentiation of endocannabinoid signaling results from an increase in the number of presynaptic cannabinoid type 1 receptors associated with cholecystokinin-containing perisomatic inhibitory inputs, without an effect on the endocannabinoid-mediated inhibition of glutamate release. These results demonstrate a selective, long-term increase in the gain of endocannabinoid-mediated retrograde signaling at GABAergic synapses in a model of a human neurological disease.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / physiology
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Animals
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Blotting, Western
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Cannabinoid Receptor Modulators
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Cells, Cultured
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Chromatography, High Pressure Liquid
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Disease Models, Animal
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Electric Stimulation
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Endocannabinoids
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Excitatory Amino Acid Antagonists / pharmacology
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Fatty Acids, Unsaturated / metabolism*
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Hippocampus / drug effects
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Hippocampus / physiopathology
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Hyperthermia, Induced
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Immunohistochemistry
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Mass Spectrometry
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Microscopy, Electron
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Neuronal Plasticity / physiology*
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Neurons / physiology*
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Patch-Clamp Techniques
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Presynaptic Terminals / metabolism
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Presynaptic Terminals / ultrastructure
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Rats
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Rats, Sprague-Dawley
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Receptors, Cannabinoid
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Receptors, Drug / antagonists & inhibitors
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Receptors, Drug / metabolism
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Seizures, Febrile / physiopathology*
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Synaptic Transmission / physiology*
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gamma-Aminobutyric Acid / metabolism
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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Fatty Acids, Unsaturated
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Receptors, Cannabinoid
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Receptors, Drug
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gamma-Aminobutyric Acid