Statins are agents commonly used in the clinic to treat hyper-cholesterolemia, however little is known regarding their effects on neuronal function. Chronic treatment with simvastatin was shown to improve learning and memory in behavioural tasks (Li et al., 2006). The aim of this research was to investigate acute and chronic effects of simvastatin on synaptic transmission, paired pulse facilitation (PPF) and long-term potentiation (LTP) in the CA1 region of the hippocampus. Transverse hippocampal slices (400μm thick) were prepared from C57 black6J mice. EPSPs were recorded in the CA1 region. Paired pulse stimuli were applied at an interval of 50ms. Fibre volleys were evoked in the presence of DNQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione) by stimulating the alveus and recording in the CA1 cell body region. Baseline stimuli were applied at a frequency of 0.033 Hz, (0.1ms) and recordings made for 20min prior to application of simvastatin or LTP induction. LTP was induced using 100 or 200 Hz. 100 Hz protocol: Two stimulus trains at 100Hz for one second applied 30s apart. 200 Hz protocol: Two sets of ten trains of ten stimuli at 200Hz, 2s inter-train interval; 30s between sets. Control LTP (100Hz) measured at 60min in slices from 8week old animals (young) measured 169.0 ± 11.2% (n=13), while that induced using 200Hz measured 166.9 ± 6.5% (n=10). Acute application of simvastatin (35μM) caused a significant increase in the EPSP slope to 154.4 ± 12.3%, (p<0.05, n=12) measured at 35 min compared to vehicle (105.3 ± 3.6% n=4) whereas 10μM simvastatin did not increase the EPSP slope (118 ± 6%; n=4) significantly. Simvastatin also decreased the PPF ratio (1.47 ± 0.06 to 1.30 ± 0.06; p<0.01, n=12) at 35min. LTP (100 or 200Hz) measured from baseline prior to induction in the presence of simvastatin (35μM) was decreased significantly compared to control (133.2 ± 4.8% n=8 and 132.9 ± 10.9%, respectively n=6). Following chronic simvastatin treatment (0.04%, in the diet for 6 months), LTP (100Hz) induced in slices from 18 month old animals measured 158.3 ± 6.9% (n= 7) and was not significantly different to levels recorded in slices from 8 or 16 month old animals (177.8 ± 9.0%, n=7 and 175.2 ± 16%, n=8 respectively). In slices from young animals treated acutely with simvastatin (35μM), fibre volley amplitude increased to 137.3 ± 5.7% (n=9, p< 0.001) compared to vehicle control 105.3 ± 7.3% (n=4). Fibre volleys recorded in slices from chronically treated animals increased to 108.7 ± 7% following acute simvastatin (35μM) application which was not significantly different from vehicle control. Acute simvastatin appears to increase neurotransmitter release, possibly by increasing fibre volley amplitude while chronic treatment has no effect on LTP.