Photolytically released nitric oxide produces a delayed but persistent suppression of LTP in area CA1 of the rat hippocampal slice.
1. We have used flash photolysis of a caged form of nitric oxide (NO), potassium pentachloronitrosylruthenate (K2Ru(NO)Cl5), to apply known concentrations of NO, with a high degree of temporal resolution, to hippocampal slices prepared from juvenile male rats maintained in an interface recording chamber. 2. Photolytically released NO (1-4.5 microM) from bath applied caged NO reduced the magnitude of long-term potentiation (LTP) in a concentration-dependent manner. This effect was abolished in the presence of the NO scavenger haemoglobin. NO had no effect on pre-established LTP. 3. Exposure to photolytically released NO had no effect on normal fast synaptic transmission, but did result in depression of N-methyl-D-aspartate (NMDA) receptor-mediated transmission recorded using extracellular electrodes. The onset of NO-induced depression was relatively slow, taking >40 s to manifest itself, and several minutes to achieve maximum depression (t approximately 70 s). NO-induced depression persisted for more than 2 h after photolysis. The time courses of the action of NO on NMDA receptor-mediated responses and its action on the induction of LTP were similar. 4. These results suggest that released NO may play a role in determining the subsequent threshold for the induction of LTP at Schaffer-commissural synapses through a reduction in the efficacy of NMDA receptor function when repeated conditioning trains are used.
Murphy
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KP
Division of Neurophysiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.kpsjm2@cam.ac.uk
Bliss
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TV
D000818:Animals; D004594:Electrophysiology; D006454:Hemoglobins / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010782:Photolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors
D006454:Hemoglobins; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide