Low-Frequency Electrical Stimulation Reduces the Impairment in Synaptic Plasticity Following Epileptiform Activity in Rat Hippocampal Slices through α1, But Not α2, Adrenergic Receptors.

Low frequency stimulation (LFS) has anticonvulsant effect and may restore the ability of long-term potentiation (LTP) to the epileptic brain. The mechanisms of LFS have not been completely determined. Here, we showed that LTP induction was impaired following in vitro epileptiform activity (EA) in hippocampal slices, but application of LFS prevented this impairment. Then, we investigated the involvement of α-adrenergic receptors in this effect of LFS. EA was induced by increasing the extracellular K+ concentration to 12 mM and EPSPs were recorded from CA1 neurons in whole cell configuration. EA increased EPSP amplitude from 6.9 ± 0.7 mV to 9.6 ± 0.6 mV. For LTP induction, the Schaffer collaterals were stimulated by high frequency stimulation (HFS; two trains of 100 pulses, 100 Hz at the interval of 20 s). The application of HFS resulted in 40.9 ± 2.3% increase in the amplitude of EPSPs. However, following EA, HFS could not produce any significant changes in EPSP amplitude. Administration of LFS (1 Hz, 900 pulses) to Schaffer collaterals at the beginning of EA restored LTP induction to the hippocampal slices and HFS increased the EPSPs amplitude up to 41.7 ± 3.1% of baseline. When slices were perfused by prazosin (α 1 -adrenergic receptor antagonist; 10 μM) before and during LFS application, LFS improvement on LTP induction was reduced significantly. Perfusion of slices by yohimbine (α 2 -adrenergic receptor antagonist; 5 μM) had no effect on LFS action. Therefore, it may be concluded that following epileptiform activity, LFS can improve the impairment of LTP generation through α 1 , but not α 2 , adrenergic receptor activity. Unlabelled Image • High-K + induced epileptiform activity (EA) was induced in hippocampal slices. • EA lead to impairment in LTP generation by high frequency stimulation. • LFS reduced the duration of EA and returned the ability of LTP induction. • This effect of LFS was mediated through α 1 but not α 2 receptors activity. [ABSTRACT FROM AUTHOR]