The Na+/H+ exchanger modulates long-term potentiation in rat hippocampal slices

Although present in great variety in the brain, the role of Na⁺/H⁺ exchangers (NHEs) in hippocampal plasticity is still unknown and the effect of NHE inhibition on long-term potentiation (LTP) has not been studied yet. As it is conceivable that NHE inhibitors may severely affect mechanisms that are considered to underlie learning and memory we investigated whether the broad-spectrum NHE inhibitor 5′-(N-ethyl-N-isopropyl)-amiloride (EIPA, 10 μM) influences LTP induced by different stimuli based on a theta burst in interface hippocampus slices from 7–8-week-old Wistar and 30-month-old Fischer 344/Brown–Norway F1 hybrid (F344/BN) rats. EIPA did not affect basal synaptic transmission, paired pulse inhibition, or LTP induced by a weak stimulus, but improved the maintenance of the LTP of the population spike induced by a strong tetanus. Our data suggest that NHE activity serves as a negative feedback mechanism to control neuronal excitability and plasticity in both young and senescent animals.