Temporal Lobe Epilepsy is the most common form of epilepsy – a neurological disorder characterised by abnormal synchronous neuronal activity. High frequency activity (HFA) can be characterised into ripples and fast ripples. Ripples are physiological and have a frequency around 100-200Hz; fast ripples are pathological have a frequency of around >250Hz[1]. As fast ripples are a biomarker for the epileptogenic zone[2] and the ventral hippocampus is more susceptible to epileptic activity[3], we hypothesised that changes in HFA could explain the increased epileptogenicity. Previous studies have demonstrated that the ventral and dorsal regions of the hippocampus differ intrinsically[4]; with an increase in functional Ih channels[5]. We therefore examined the dorso-ventral profile of HFA in the hippocampus. Adult VGAT-Venus A rats were anaesthetised with 3mg/kg medotomidine and 300mg/kg ketamine using I.P. injection. After cervical dislocation or intracardial perfusion with sucrose aCSF, 400 μm sections containing the dorsal and ventral hippocampus were prepared. Extracellular field potentials were recorded from the stratum pyramidale of CA3b. Seizure-like discharges with HFA were induced by increasing the potassium concentration to 8-12mM. Data is given as the median±IQR.The high potassium model generated HFA which was seen superimposed on sharp waves. The average K+ concentration required to generate HFA was not different in the ventral and dorsal hippocampus (8±2 mM and 8.25±1.5 mM, respectively; p=0.81, Mood’s Median Test). The average frequency and power of the HFA was analysed for 9 ventral slices and 8 dorsal slices (from 9 animals). The frequency of HFA was lower in dorsal slices than in ventral slices (187±38 Hz and 246±53 Hz, respectively; p=0.002, Mann-Whitney U test). The power of the HFA was also reduced (0.15±0.78 mV2 and 4.57±7.90 mV2, respectively; p=0.01, Mann-Whitney U test). The Ih channel blocker, ZD7288 (10μM), significantly reduced the average frequency of HFA (Control – 219.5±77.2, ZD7288 – 214.1±76.0 Hz; p=0.04, Wilcoxon signed rank test). The HFA power was not affected by ZD7288.These data show that HFA is more pronounced in the ventral hippocampus than in the dorsal, which supports previous observations of increased excitability and susceptibility to epileptic activity in the ventral hippocampus. The underlying mechanisms that contribute to this increased excitability are yet to be determined and the contribution of Ih channels remains unclear.
Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCA062
Poster Communications: Understanding the dorso-ventral profile of epileptic high frequency activity
E. J. Rawlins1, S. Hannan1, E. M. Fox1, G. Morris1, A. D. Powell1
1. School of Clinical & Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.
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