Temporal Lobe Epilepsy is the most common form of epilepsy – a neurological disorder characterised by abnormal excitation and synchronisation of neuronal networks. High frequency activity (HFA) is defined as network activity with frequency of over 100 Hz and is a biomarker for the epileptic hippocampus. The underlying mechanism is unknown, but it is hypothesised that interneurons, which are capable of firing action potentials (APs) at frequencies in the HFA range, could synchronise local pyramidal cell activity. High frequency interneuronal firing imposes synchronous IPSPs upon on a population of pyramidal cells, creating temporal windows in which they can fire. This could lead to synchronised high frequency population events. Using the VGAT-Venus A strain of rats that selectively express the fluorescent Venus protein in interneurons, we have examined the role of hippocampal interneurons in the genesis of HFA. Adult VGAT-Venus A rats were anaesthetised with 0.24mg/kg medotomidine and 58.2mg/kg ketamine via I.P. injection before transcardial perfusion with sucrose ACSF, and 300 μm horizontal brain slice preparation. Extracellular recordings were made from stratum pyramidale (SP) in hippocampal region CA3b. Interictal-like discharges (ILDs) were induced by superfusion of the slices with high potassium (9mM). Following induction of ILDs, whole-cell patch clamp recordings were made from interneurons, irrespective of location, which were identified using fluorescence microscopy. Data is given as the mean±SEM. Superfusion of high potassium generated ILDs (frequency = 0.72±0.04Hz; n=11), on which HFA (190.6±9.8 Hz; n=10) was superimposed. Interneurons were divided into four categories, as defined by their firing pattern. Group 1 neurons fired throughout ILDs and correlated with HFA (mean max. firing frequency = 207.5; n=2), whilst group 2 neurons fired throughout ILDs but were not correlated with HFA (182.50±20.4 Hz; n=4). Group 3 neurons fired a single AP on each ILD (n=2) whereas group 4 neurons fired randomly except for 2-3 APs at the onset of each ILD (120±31.8 Hz; n=3). Those neurons whose activity correlated with HFA were found in SP and stratum oriens and those which fire single APs were found in SP and stratum radiatum. Interneurons which are capable of maintaining HFA frequency firing, but do not correlate with HFA, were found throughout the layers of the hippocampus. These results show that a sub-population of interneurons correlate with HFA and are candidates for pacing this activity. Pharmacological or electrophysiological manipulation of candidate cells has the potential to affect epileptic field activity by reducing the pathological synchronisation of pyramidal cell activity.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD112
Poster Communications: Investigating the role of interneurons in epileptic high frequency activity
G. Morris1, P. Jiruska2, W. Chang1, A. D. Powell1, J. G. Jefferys1
1. Neuronal Networks, University of Birmingham, Birmingham, United Kingdom. 2. Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences of Czech Republic, Prague, Czech Republic.
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Where applicable, experiments conform with Society ethical requirements.