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The Effect of Gabaergic Neurotransmission on the Seizure-Related Activity of the Laterodorsal Thalamic Nuclei and the Somatosensory Cortex in a Genetic Model of Absence Epilepsy Publisher Pubmed



Jafarian M1, 2 ; Modarres Mousavi SM2, 3 ; Rahimi S4, 5 ; Ghaderi Pakdel F6 ; Lotfinia AA2 ; Lotfinia M2 ; Gorji A2, 5, 7
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Authors Affiliations
  1. 1. Brain and Spinal Cord Injury Research Center, Neurosciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
  3. 3. Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
  4. 4. Department of Genetics and Pharmacology, Institute of Molecular and Cellular Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
  5. 5. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  6. 6. Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  7. 7. Epilepsy Research Center, Department of Neurosurgery, Westfalische Wilhelms-Universitat Munster, Munster, Germany

Source: Brain Research Published:2021


Abstract

The present study aimed to investigate the alterations of the GABAergic system in the laterodorsal nucleus (LDN) of the thalamus and the somatosensory cortex (SC) in an experimental model of absence seizure. The effects of pharmacological manipulation of both GABAA and GABAB receptor subunits in the LDN on the generation of spike-wave discharges (SWD) were evaluated. The experiments were carried out in four groups of both WAG/Rij and Wistar rats with 2 and 6 months of age. The expressions of various GABA receptor subunits were studied in the LDN and SC. Furthermore, recordings of unit activity from the LDN and electrocorticography were simultaneously monitored before, during, and after the application of GABAA and GABAB antagonists in the LDN. The generation of SWD in the older WAG/Rij rats was associated with significant alterations in the expression of GABAARα1, GABAARβ3, and GABABR2 subunits in the LDN as well as GABAARα1, GABAARβ3, GABAARγ2, and GABABR2 subunits in the SC. Furthermore, the occurrence of SWD was associated with a significant reduction of gene expression of GABAARα1 and increase of GABAARβ3 in the LDN as well as reduction of GABAARα1, GABAARβ3, GABAARγ2, and GABABR2 in the SC. The microionthophoretic application of the GABAA antagonist bicuculline resulted in a significant increase in the population firing rate of LDN neurons as well as the mean number and duration of SWD. The application of the GABAB antagonist CGP35348 significantly increased the population firing rate of LDN neurons but decreased the mean number of SWD. Our data indicate the regulatory effect of the GABAergic system of the LDN and SC in absence seizures. © 2021 Elsevier B.V.
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