Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures.
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.
Chen
Kang
K
Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA.
Ratzliff
Anna
A
Hilgenberg
Lutz
L
Gulyás
Attila
A
Freund
Tamás F
TF
Smith
Martin
M
Dinh
Thien P
TP
Piomelli
Daniele
D
Mackie
Ken
K
Soltesz
Ivan
I
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D063385:Cannabinoid Receptor Modulators; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004558:Electric Stimulation; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D013058:Mass Spectrometry; D008854:Microscopy, Electron; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D003294:Seizures, Febrile / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; D005231:Fatty Acids, Unsaturated; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D005680:gamma-Aminobutyric Acid