The polyamine, spermine (SPM) is an endogenous regulator of neurotransmission (Nature 401(1999)594; J. Neurophysiol. 93(2005)2634). SPM is mainly stored in glia, not in neurons (Glia 19(1997)171) and SPM levels in astrocytes vary with the functional state of glia (SFN 2004 No. 284.7). The purpose of the present study was to determine the effects of exogenous SPM and other treatments that release SPM from glia in comparison to the effect of the GluR2 lacking AMPA receptor antagonist IEM-1460 on the electrical activity of hippocampal interneurons. Solutions were applied by bath perfusion so that all cells in the slice were exposed. We found populations of interneurons in both s. oriens and s. radiatum that responded to exogenous SPM (200 µM) with hyperpolarization accompanied by a decreased firing rate (32%), with depolarization accompanied by increase in firing frequency (16%) or with no effect (52%). IEM-1460 (10 µM) always produced the same effect as SPM. Furthermore, we found that glial specific treatmen...