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.