Deep Brain Stimulation of the Ventral Pallidum Attenuates Epileptiform Activity and Seizing Behavior in Pilocarpine-Treated Rats

Background: Brain stimulation is effective for people with intractable epilepsy. However, modulating neural targets that provide greater efficacy to more individuals is still needed. Objective/hypothesis: We investigate whether bilateral deep brain stimulation of the ventral pallidum (VP-DBS) has potent seizure control in pilocarpine-treated rats. Methods: VP-DBS (50 Hz) was applied prior to generalized forebrain seizures or after generalized brain stem seizures manifested. Behavioral seizures were assessed using a modified Racine scale. In vitro and in vivo electrophysiological techniques were employed to identify how VP-DBS affects proximal and distal neuronal activity. The open field test was used to see if acute and chronic VP-DBS affected gross motor function or arousal state. Parametric and non-parametric statistics with post-hoc analysis were performed. Results: VP-DBS prior to pilocarpine prevented behavioral forebrain and brainstem seizures in most animals (n = 15). VP-DBS after brainstem seizures emerged prevented or reduced the appearance of subsequent behavioral brainstem seizures (n=11). VP-DBS attenuated epileptiform activity in the hippocampus (n = 5), but not in the primary somatosensory cortex (S1) (n = 4) in vivo. Electrical stimulation in the VP increased VP GABAergic neuronal firing activity from 3.1 +/- 1.4 Hz to 7.6 +/- 1.7 Hz (n = 8) in vitro and reduced substantia nigra reticulata and superior colliculus neuronal spiking activity from 25.4 +/- 3.3 Hz to 18.2 +/- 1.4 Hz (n = 6) and 18.2 +/- 1.4 Hz to 11.0 +/- 1.1 Hz (n =18), respectively, in vivo. Conclusion: VP-DBS can be a novel and potent therapeutic approach for individuals with intractable epilepsy. (C) 2016 Elsevier Inc. All rights reserved.