High frequency activity (HFA) is a phenomenon where neuronal networks oscillate at frequencies faster than 100 Hz. Physiological HFA (‘ripple band’) is implicated in learning and memory and has a frequency of around 100-200 Hz. Network ripples in the hippocampus in vivo are tightly phase-locked to the firing of certain interneurons, implying a causative relationship and a pacemaker role for the interneuron within the oscillation (Csicsvari et al 99;Ylinen et al 95). HFA that is faster than 200 Hz (‘fast ripple band’) is unique to the epileptic brain (Bragin et al 99). The mechanism underlying fast ripples is unknown and could give an insight into the pathophysiology of epilepsy, with the potential to identify new therapeutic targets. This work examined the relationship between interneuron firing and HFA in the acute high potassium model of epilepsy in vitro.300 µm horizontal brain slices were prepared from adult VGAT-Venus A rats (Uematsu et al 08), following cardiac perfusion with sucrose ACSF. Rats were anaesthetised with 0.24mg/kg medotomidine and 58.2mg/kg ketamine via I.P. injection. Epileptic-like activity, including HFA, was induced by bath perfusion of 9mM potassium. Field activity was recorded from stratum pyramidale in hippocampal CA3b and simultaneous single-cell recordings were made from interneurons, as identified by the fluorescent Venus transgene. The phase relationship between HFA cycles and interneuronal action potentials was determined using a custom made MatLab script; the significance of these relationships was determined using Rayleigh statistics (α=0.05). Averages are presented as mean±SEM.Perfusion of 9mM potassium caused epileptic-like discharges, including HFA, in 83 out of 131 slices. Traces where HFA was acquired simultaneously with successful single-cell recordings were analysed further (n=36). Peak HFA frequency was normally distributed (Kolomogorov-Smirnov test, p=>0.05), with a mean of 216±5 Hz, and spanned both the ripple (n=8) and fast ripple (n=28) bands. Using interneuronal action potentials as a reference, 11 cells showed significant phase correlation with HFA cycles. Despite the unimodal distribution of HFA frequencies, ripples were significantly more likely than fast ripples to be correlated with interneuronal activity (Fisher’s exact test, p=<0.001).This suggests a fundamental mechanistic difference between ripple and fast ripple band activity, which hints at a failure of interneurons to modulate high frequency activity in the epileptic brain.