Abstracts

Rationale: The mechanisms regulating the spatial distribution of epileptiform discharges in the adult neocortex have been studied less than in the hippocampus of young animals. Seizures are known to induce a fall in [Ca] and increase in [K] in the extracellular milieu: these changes of ionic environment are known to affect the neurophysiological components of seizures by depressing synaptic transmission and enhancing membrane excitability. This paper studies the effect of perfusing rat adult neocortex slices with low [Ca] ,high [K] solutions, characterizing the spatial distribution of discharges through Multiple Electrodes Arrays (MEA) to define sites of discharge origin, propagation pathways and spatial spread. Methods: We recorded through MEA with 59 electrodes from adult rats somatosensory slices perfused with solutions containing low [Ca] and high [K]. We also compared epileptiform activity evoked by 4-Aminopyridine (4-AP) and no Mg with that evoked by 4-AP, no Mg, low [Ca] and high [K]. Results: Perfusion through media with low [Ca] and high [K] by itself did not evoke detectable epileptiform activity. Perfusion with 4-AP and no Mg evoked discharges consisting of recurrent isolated sharply contoured voltage transients, consistent with interictal discharges. Occasionally, these were followed by rhythmic repetitive sharp waves with a progressive evolution in voltage and frequency, consistent with ictal-like events. Switching perfusion to a medium with 4-AP, no Mg, low [Ca] and high [K] did not affect either amplitude, rate, spatial spread of isolated discharges or even the duration of seizures. Low [Ca] high [K] converts isolated discharges induced by 4-AP into rhythmic repetitive discharges, jumpstarting them into a non-evolving high voltage rhythm. Conclusions: In the adult somatosensory cortex a low [Ca] and high [K] solution by itself is not a condition sufficient to initiate epileptiform discharges. Rather, low [Ca] high [K] can modulate discharges initiated by another pro-convulsant stimulus. When discharges are initiated by 4-AP, low [Ca] high [K] neither enhances recruitment into a broader zones of epileptic hyper-synchrony nor increases rate or maximal voltage of discharges. Thus, in the neocortex Ca and K extracellular homeostasis selectively modulates the transition interictal-to-ictal. The gradual accumulation of extracellular [K] may underly the frequency and voltage evolution typical of an ictal pattern. Funding: Start-up funding from the University of Utah to RS