Extracellular Voltage Clamp Completely Suppresses Generation of Epileptiform Activity In-vitro
Abstract number :
1.043
Submission category :
1. Basic Mechanisms / 1D. Mechanisms of Therapeutic Interventions
Year :
2022
Submission ID :
2204251
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Muthumeenakshi Subramanian, BE – Case Western Reserve University; Chia-Chu Chiang, PhD – Post Doctoral Fellow, Biomedical Engineering, Case Western Reserve University; Diminique Durand, PhD – EL Lindseth Professor of Biomedical Engineering, Biomedical Engineering, Case Western Reserve University
Rationale: Neural recruitment in epilepsy occurs in part due to electric field (ephaptic) coupling in addition to synaptic mechanisms. We have shown that neural activity like theta waves, epileptic spikes and seizures can cross a physical transection in vivo using electric fields thus propagating independent of synaptic transmission. Hence, controlling the local electric field could suppress or cancel the generation of these epileptic events. We tested the hypothesis that clamping the local extracellular electric fields in a known focus can prevent the generation of epileptic spikes and seizures.
Methods: 4-Aminopyridine (4-AP) was used to induce spontaneous epileptic spikes and seizures in an in vitro experimental setup using longitudinal hippocampal slices from four mice. 100 % of the epileptic activity originated at the temporal region and propagated to the septal region of the slices thereby establishing the existence of a focus in the temporal end of the tissue. A recording electrode (Rec1) was placed in the cell layer within the focus to detect the generation of the epileptic activity. Another recording electrode (Rec2) was placed in the septal region to observe the propagation of the activity along the longitudinal direction. In line with Rec1, two stimulating electrodes (S1) and (S2) were placed outside the slice in the transverse direction at the edge of the Temporal region. An extracellular voltage clamp system was connected to Rec1 and S1-2 and applied a feedback current to maintain the voltage at R1 equal to zero.
Results: When the feedback circuit was turned “on”, the electric field produced by the applied current cancelled the local extracellular electric field involved in the generation of the epileptic events as evidenced by the clamp achieving 100% suppression of both epileptic spikes and seizure events as observed by Rec1. No spikes or seizures were observed in the septal region when the clamp was “on” with Rec2 also showing complete suppression of epileptiform activity. When the clamp was turned off both the spikes and seizure events recovered.
Conclusions: An extracellular voltage clamp applied to a known epileptic focus can completely supress the generation of the epileptiform activity and prevent its propagation away from the focus. Although the spatial extent of the control is currently limited to the region around the recording site, this method could be effective to control seizure generation in a small known focus.
Funding: NIH 1R01NS121084 and RES226994
Basic Mechanisms