NITRIC-OXIDE SIGNALING IS REQUIRED FOR THE GENERATION OF ANOXIA-INDUCED LONG-TERM POTENTIATION IN THE HIPPOCAMPUS

The involvement of nitric oxide in anoxia-induced long-term potentiati on (anoxic LTP) of synaptic transmission was investigated in CA1 neuro ns of rat hippocampal slices using intracellular recording techniques in vitro. In response to superfusion of an anoxic artificial cerebral spinal fluid saturated with 95% N-2-5% CO2, the excitatory postsynapti c potential (EPSP) generated in hippocampal CA1 neurons by stimulation of the Schaffer collateral/commissural afferent pathway was completel y abolished within 10 min of anoxia. On return to reoxygenated medium, the EPSP returned to the control value within 10 min and was subseque ntly and progressively potentiated to reach a plateau 15-20 min after return to oxygen. This anoxia-induced persistent increase in synaptic transmission lasted for more than 1 h. Application of the nitric oxide synthase inhibitors 7-nitroindazole (7-NI) or L-N-6-nitroarginine (NO ARG) produced no effects on the baseline EPSP amplitude, but effective ly attenuated the anoxic LTP, The inhibitory effects of both 7-NI and NOARG on the anoxic LTP were blocked by L-arginine, a substrate for ni tric oxide synthase, These results suggest that nitric oxide is requir ed for the generation of anoxia-induced LTP of glutamatergic synaptic transmission in the CA1 region of the rat hippocampus.