Muthumeenakshi Subramanian working in Dr Dominique Durand laboratory has won a travel awards and honnorarium to the the 9th Brain Initiative conference in Bethesda. Jun 21-13 2023
(https://braininitiative.nih.gov/News-Events/event/9th-annual-brain-initiative-meeting)
Extracellular voltage clamp suppresses epileptic activity in mice hippocampus
Electric field coupling plays an important role in recruiting neurons in epilepsy causing the interictal spikes and seizure events to propagate in the tissue. Electric fields have been shown to be involved in neural activity such as theta waves, epileptic spikes, and seizures. The propagation by electric field coupling is independent of synaptic transmission, propagating even across a physical transection in in-vitro and in-vivo experiments. Therefore, controlling the local electric field could potentially suppress or prevent the generation of epileptic events. To test this hypothesis, I clamped the local extracellular electric fields in a known focus using an extracellular voltage clamp system.
Spontaneous epileptic spikes and seizures were induced using 4-aminopyridine (4-AP) in longitudinal hippocampal slices from four mice. A temporal focus was identified, from which all epileptic activity originated and propagated to the septal region of the slices. A recording electrode (Rec1) was placed in the focus to detect the generation of epileptic activity, and another recording electrode (Rec2) in the septal region to observe the propagation of activity along the longitudinal direction. Two stimulating electrodes (S1 and S2) were placed at the edge of the slice in the transverse direction at the edge of the temporal region, in line with Rec1.
When the extracellular voltage clamp system was turned "on," a feedback current was applied to maintain the Rec1 voltage at zero, which cancelled the local extracellular electric field involved in the generation of epileptic events. The clamp completely suppressed both epileptic spikes from baseline 93.8 ± 36.9 to 0 spikes in 9 slices, and seizure events from baseline 8.75 ± 5.5 to 0 seizures in 4 slices, as observed by Rec1. Furthermore, no spikes or seizures were observed in the septal region, Rec2 also showed complete suppression of propagation of epileptiform activity. When the clamp was turned "off," the spikes and seizure events recovered completely in both Rec1 and Rec2.
In conclusion, although the spatial extent of the clamp is unknown, this study effectively shows that applying an extracellular voltage clamp to a known small epileptic focus can completely suppress the generation of epileptiform activity and prevent its propagation away from the focus. This finding has implications for potential therapeutic interventions in epilepsy.