Electrophysiological imaging of epileptic brain slices reveals pharmacologically confined functional changes

Abstract Microelectrode arrays (MEAs) are employed to study extracellular electrical activity in neuronal tissues. Neverthe-less, commercially available MEAs provide a limited number of recording sites and do not allow a precise identifi-cation of the spatio-temporal characterization of the recorded signal. To overcome this limitation, high density MEAs, based on CMOS technology, were recently developed and validated on dissociated preparations (Ber-dondini et al. 2009). We show the platform capability to record extracellular electrophysiological signal from 4096 electrodes arranged in a squared area of 2.7 mm x 2.7 mm with inter-electrode distance of 21 µm at a sampling rate of 7.7 kHz/electrode. Here, we demonstrate the performances of these platforms for the acquisition chemi-cally evoked epileptiform activity from brain slices. Moreover the high spatial resolutions allow us to estimate the effect of drugs in spatially modulating Inter-Ictal ((I-IC) activity. 1 Introduction Electrophysiological recording of neuronal activ-ity in slices is a common experimental method for in-vestigating complex brain processing circuits, brain plasticity or neuropharmacology. To this end, it is cru-cial to enable recordings of electrophysiological activ-ity from large neuronal populations at sufficient spa-tial and temporal resolution, thus making possible to localize and track electrically or chemically evoked neuronal activity and to identify induced functional changes. Conventional electrophysiological include the use of electrodes and light-imaging methods to re-cord action potentials from multiple single neurons as well as local field potentials generated by neuronal ensembles. Patch-clamp and field electrodes, ap-proaches based on micro-positioned single glass pi-pettes, enable intracellular or extracellular recordings respectively, from single neurons or from neuronal populations surrounding the electrode respectively. Optical imaging based on fluorescent Ca2+ indicators [1] or voltage sensitive dyes (VSDs) [2, 3] are the current choice for spatially resolving electrical activity in the brain, but this approach suffers a modest tempo-ral resolution due to sampling frequencies in the range of 1-3 kHz. Moreover, this approach does not offer a high signal to noise ratio and is not suited to record continuously for long periods of time (usually it can records for few seconds after a triggered electrical stimulus). Consequently, these recording perform-ances are not sufficient to effectively track the electri-cal activity propagations over large areas of the brain tissue in real time, either due to insufficient spatial or temporal resolutions.