Cellular Mechanisms Underlying Antiepileptic Effects of Low- and High-Frequency Electrical Stimulation in Acute Epilepsy in Neocortical Brain Slices In Vitro

Abstract

Schiller Y, Bankirer Y. Cellular mechanisms underlying antiepileptic effects of low-and high-frequency electrical stimulation in acute epilepsy in neocortical brain slices in vitro. J Neurophysiol 97: 1887J Neurophysiol 97: -1902J Neurophysiol 97: , 2007. First published December 6, 2006; doi:10.1152/jn.00514.2006. Approximately 30% of epilepsy patients suffer from drug-resistant epilepsy. Direct electrical stimulation of the epileptogenic zone is a potential new treatment modality for this devastating disease. In this study, we investigated the effect of two electrical stimulation paradigms, sustained low-frequency stimulation and short trains of high-frequency stimulation, on epileptiform discharges in neocortical brain slices treated with either bicuculline or magnesium-free extracellular solution. Sustained low-frequency stimulation (5-30 min of 0.1-to 5-Hz stimulation) prevented both interictal-like discharges and seizure-like events in an intensity-, frequency-, and distance-dependent manner. Short trains of high-frequency stimulation (1-5 s of 25-to 200-Hz stimulation) prematurely terminated seizure-like events in a frequency-, intensity-, and duration-dependent manner. Roughly one half the seizures terminated within the 100-Hz stimulation train (P Ͻ 0.01 compared with control), whereas the remaining seizures were significantly shortened by 53 Ϯ 21% (P Ͻ 0.01). Regarding the cellular mechanisms underlying the antiepileptic effects of electrical stimulation, both low-and high-frequency stimulation markedly depressed excitatory postsynaptic potentials (EPSPs). The EPSP amplitude decreased by 75 Ϯ 3% after 10-min, 1-Hz stimulation and by 86 Ϯ 6% after 1-s, 100-Hz stimulation. Moreover, partial pharmacological blockade of ionotropic glutamate receptors was sufficient to suppress epileptiform discharges and enhance the antiepileptic effects of stimulation. In conclusion, this study showed that both lowand high-frequency electrical stimulation possessed antiepileptic effects in the neocortex in vitro, established the parameters determining the antiepileptic efficacy of both stimulation paradigms, and suggested that the antiepileptic effects of stimulation were mediated mostly by short-term synaptic depression of excitatory neurotransmission.

Effects of hippocampal high‐frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats

“…These inhibitory effects of HFS have been associated with reduction in excitability of neurons, increased inhibitory neurotransmission, and depression of excitatory neurotransmission (Boraud et al, 1996;Durand and Bikson, 2001). In contrast, other HFS studies indicate an increase in neuronal excitation (Schiller and Bankirer, 2007) that desynchronize during prolonged stimulation leading to the illusion of conduction block (Jensen and Durand, 2009). It is possible that a balanced combination of excitation and inhibition may drive the effects of HFS in memory process (McIntyre et al, 2004), an idea that is supported by the enhanced release of both, excitatory and inhibitory amino acids as consequence of HFS.…”

Possibly lifesaving, noninvasive, EEG‐guided neuromodulation in anesthesia‐refractory partial status epilepticus

“…Since a low stimulation frequency of 0.5 Hz has often been used and seems to be most effective [3,4], this was chosen in the present study. Important aspects are likely to be the degree to which the pathologic activity is localized and how well the treatment is adapted to this [10]. The efficacy is also likely to increase if the treatment is initiated early in the epileptic process; for the separate seizure episode, for the status epilepticus as such, and for the epileptogenesis thereby induced [11][12][13].…”

Potassium diffusive coupling in neural networks

“…Historically, studies have emphasized the effect of electrical stimulation on activity at the cell body, with suppression of somatic activity during stimulation predominating (figure 7a,b;D'Ambrosio et al 1998;Beurrier et al 2001;Bikson et al 2001;Garcia et al 2003;Lee et al 2003;Richardson et al 2003;D'Ambrosio 2004). Recent studies have shown that electrical stimulation also generates changes in axonal activity (Raastad & Shepherd 2003;Soleng et al 2004;Meeks et al 2005;Iremonger et al 2006;De Col et al 2008) including a depression of excitatory synaptic currents (Iremonger et al 2006;Schiller & Bankirer 2007), and conduction blockade in the PNS (Kilgore & Bhadra 2006;Ragnarsson 2007;Tai et al 2007) and in the CNS (figure 7c; Jensen & Durand 2007). Thus, changes in neural activity induced by electrical stimulation provide a means to modulate abnormal communication at several levels within the target network.…”