title: Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS.
abstract: Long-term potentiation (LTP) is a persistent increase in synaptic strength implicated in certain forms of learning and memory. In the CA1 region of the hippocampus, LTP is thought to involve the release of one or more retrograde messengers from the postsynaptic cell that act on the presynaptic terminal to enhance transmitter release. One candidate retrograde messenger is the membrane-permeant gas nitric oxide (NO), which in the brain is released after activation of the neuronal-specific NO synthase isoform (nNOS). To assess the importance of NO in hippocampal synaptic plasticity, LTP was examined in mice where the gene encoding nNOS was disrupted by gene targeting. In nNOS- mice, LTP induced by weak intensity tetanic stimulation was normal except for a slight reduction in comparison to that in wild-type mice and was blocked by NOS inhibitors, just as it was in wild-type mice. Immunocytochemical studies indicate that in the nNOS- mice as in wild-type mice, the endothelial form of NOS (eNOS) is expressed in CA1 neurons. These findings suggest that eNOS, rather than nNOS, generates NO within the postsynaptic cell during LTP.
authors.affiliation: Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
authors.forename: T J
authors.initials: TJ
authors.lastname: O'Dell
authors.forename: P L
authors.initials: PL
authors.lastname: Huang
authors.forename: T M
authors.initials: TM
authors.lastname: Dawson
authors.forename: J L
authors.initials: JL
authors.lastname: Dinerman
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
authors.forename: E R
authors.initials: ER
authors.lastname: Kandel
authors.forename: M C
authors.initials: MC
authors.lastname: Fishman
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D004727:Endothelium / Q000201:enzymology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D051379:Mice; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D017966:Pyramidal Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases