Interaction between tetanus long-term potentiation and hypoxia-induced p+otentiation in the rat hippocampus

The interaction between tetanus-induced long-term potentiation (LTP) and hypoxia-induced potentiation was investigated by performing extracellular recordings in the CA1 region of rat hippocampus using a two-pathway design. Hippocampal slices were placed in an interface chamber containing artificial cerebrospinal fluid (ACSF) solution with high magnesium concentration. Hypoxia was induced by replacing the 5% CO sub(2)-95% O sub(2) gas mixture with 5% CO sub(2)-95% N sub(2) for 2 min. Tetanus-LTP was induced with 1-s, 100-Hz current pulses. Significant hypoxia-induced potentiation of the slope of the dendritic excitatory postsynaptic potential (EPSP) was found in ACSF containing 2 mM of magnesium 2, 27 plus or minus 10% (mean plus or minus SE; n = 16; P < 0.01) with no change in the mean amplitude of the presynaptic volley. All experiments in which a stable control baseline was obtained were used for data analysis. The data show that short episodes (2 min) of hypoxia can induce LTP of the alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-mediated synaptic transmission. The present study demonstrated that after tetanus-LTP, 33 plus or minus 3% (n = 10; P < 0.01), hypoxia further potentiated the field EPSP slopes by a mean value of 16 plus or minus 5% (n = 10; P < 0.05). Moreover, using a two-pathway design, we showed that hypoxia produced similar potentiation in both the control [19 plus or minus 5%; n = 10; P < 0.01) and tetanus-induced LTP pathway, and the total potentiation produced by a combination of tetanus then hypoxia, 63 plus or minus 13% (n = 10; p < 0.01), was significantly larger (P < 0.01) than hypoxia alone. These data suggest that hypoxia-induced potentiation is additive with tetanus-LTP. Occlusion experiments were performed to verify whether the mechanisms responsible for hypoxia-induced potentiation are independent of preexisting synaptic levels induced by high-frequency stimulation. Hypoxia produced significant potentiation (23 plus or minus 7%; n = 7; P < 0.05) after successful occlusion of the LTP pathway. Therefore, because the magnitude of hypoxia-induced potentiation is both independent of preexisting synaptic levels and also additive, synaptic specificity associated with LTP is preserved. The magnitude of tetanus-LTP induced 20 min after hypoxia (15 plus or minus 4%; n = 10) was significantly smaller (P < 0.01) relative to LTP after normoxic conditions (33 plus or minus 3%; n = 10). Additionally, hypoxia blocked the transient,