Deep brain stimulation effects on learning, memory and glutamate and GABAA receptor subunit gene expression in kindled rats

Abstract

Epileptic seizures are accompanied by learning and memory impairments. In this study, the effect of low frequency stimulation (LFS) on spatial learning and memory was assessed in kindled animals and followed for one month. Fully kindled rats received LFS at 4 times (immediately, 6 h, 24 h and 30 h following the final kindling stimulation). Applying LFS improved kindled animals' performance in the Barnes maze test. This LFS action was accompanied by a decrease in NR2B gene expression, an increase in the gene expression of the α subunit of calcineurin A and an increased NR2A/NR2B ratio in kindled animals. In addition, the gene expression of the GABAA receptor γ2 subunit increased at 2-3 h after applying LFS. The increase in NR2A/NR2B ratio was also observed 1 week after LFS. No significant changes were observed one month after LFS administration. Field potential recordings in the hippocampal CA1 area showed that kindling-induced potentiation of the field EPSP slope returned to near baseline when measured 2-3 h after applying LFS.Therefore, it may be postulated that applying LFS in kindled animals reduced the seizure-induced learning and memory impairments, albeit time-dependently. In tandem, LFS prevented kindling-induced alterations in gene expression of the described proteins, which are potentially important for synaptic transmission and/or potentiation. Moreover, a depotentiation-like phenomenon may be a possible mechanism underlying the LFS action.

Effect of the closed‐loop hippocampal low‐frequency stimulation on seizure severity, learning, and memory in pilocarpine epilepsy rat model

“…Our hypothesis is based on previous reports showing that abnormal, seizure-induced synaptic potentiation impairs the new synaptic potentiation and results in memory impairment. 29,44 In this regard, it has been suggested that an abnormal plasticity may occur in mPFC communications following the strong coupling of hippocampal theta and mPFC gamma bands. 52 Although there was no significant difference in coherence of delta and theta bands during post-ictal period, calculating the ratio between post-ictal and pre-ictal has shown an increase in delta and theta coherence after DBS application.…”

“…Our hypothesis is based on previous reports showing that abnormal, seizure‐induced synaptic potentiation impairs the new synaptic potentiation and results in memory impairment. 29 , 44 In this regard, it has been suggested that an abnormal plasticity may occur in mPFC communications following the strong coupling of hippocampal theta and mPFC gamma bands. 52 …”

“…We have described this test in detail in our previous study. 29 The Barnes maze consisted of an elevated (90 cm to the floor) black acrylic circular platform, 120 cm in diameter, containing 18 holes around the periphery. The holes had uniform diameter (9 cm) and appearance, but only one hole was connected to a removable black escape box (35 cm long, 11.5 cm wide, and 10.3 cm in depth).…”

“…The Barnes maze test was used for evaluating changes in spatial learning and memory. We have described this test in detail in our previous study 29 . The Barnes maze consisted of an elevated (90 cm to the floor) black acrylic circular platform, 120 cm in diameter, containing 18 holes around the periphery.…”