Cessation of Spontaneous Burst Activity Following Application of Anti-Convulsants on Living Neural Networks Cultured on Micro-Electrode Arrays



(Abstract)One of the most prominent features of the activity of neurons in culture is the appearance of repetitive quasi-synchronized clusters of action potentials often referred to as bursts. These bursts occur every few seconds and can typically continue for 100 ms to over a second and are reminecent of epileptic seizure activity in vivo. This has led some to suggest that in vitro bursting and epilepsy my share a common cause. Since a wide variety of antiepileptic drugs (AED) exist to treat the symptoms of epilepsy (i.e. prevent or reduce seizure activity) in vivo, , one natural prediction would be that to the extent that seizures in vivo and those in vitro are similar, they should have a similar affect in vitro. That is, these AEDs should also be highly effective in modulating the burst activity in vitro as well. To test this prediction the effect of three of the most common AEDs on the market: phenytoin, ethosuximide, and valproate, were delivered to in vitro rat cortical neurons cultured on 60 channel micro-electrode arrays (MEAs). With these arrays, neural activity (single unit action potentials) at 60 sites across the network was measured before and after the delivery of each AED. Phenytoin, used for grand mal seizures, was the most effective of the three drugs eliminating spontaneous bursts entirely. Ethosuximide, used for petit mal seizures, and valproate, used for various forms of epilepsy, reduced but did not eliminate spontaneous bursts. A comparison of the network’s evoked response to single site stimulation pulses indicated that even though phenytoin had effectively eliminated spontaneous bursts, it did not eliminate bursts of activity. It did however, reduce the number of action potentials that contributed during the bursts. In contrast, Ethosuximide and valproate had no affect on either the duration or the number of action potentials with each evoked burst. Together, these findings suggest a connection between in vivo seizure and its’ in vitro analog.