The Effects of Gabapentin on Epileptic Seizures: A Computational Model
Keywords:gabapentin, epilepsy, seizure, anticonvulsant, hippocampus, voltage-gated calcium channels, cortical neurons, NMDA receptors, O-LM interneurons, pyramidal cells, basket cells, synaptic transmission, post-synaptic terminal, pre-synaptic terminal, dendritic inhibition, Local Field Potential, Raster plot, Power Spectrum Density
Anticonvulsant sedatives are commonly used to stop epileptic seizures; however, many result in significant harmful side-effects. In this paper, we explore gabapentin, an alternative anticonvulsant, as a safer, more effective treatment for epileptic seizures. The goal of our study was to determine the conditions under which gabapentin has the greatest potential to suppress epileptic seizures through its interactions with voltage-gated Ca2+ channels. First, we ran an existing network model of the CA3 region of the hippocampus. Next, we rendered the model seizure prone through impaired dendritic inhibition to pyramidal cells due to the dysfunction of O-LM interneurons. Then, we implemented gabapentin into the network as a parameter that acts as a proxy for dosage and scales the Ca2+ channel conductance in excitatory neurons. By increasing the dosage of gabapentin, the resulting Ca2+ current was decreased, inhibiting the seizure. In fact, at high doses of gabapentin, we saw seizures were significantly suppressed. Our model supports the efficacy of gabapentin as a seizure medication. However, clinical trials are needed to find appropriate dosages and side effects of the drug.
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Copyright (c) 2022 Anand Ramabadran, Vidya Desai, William Longtin, Laya Palutla; Marianne Bezaire
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