Enhanced endogenous activation of NMDA receptors in pyramidal neurons of hippocampal tissues from patients with mesial temporal lobe epilepsy: A mechanism of hyper excitation

Banerjee, Jyotirmoy; Dixit, Aparna Banerjee; Tripathi, Manjari; Sarkar, Chitra; Gupta, Yogendra Kumar; Chandra, P. Sarat

doi:10.1016/j.eplepsyres.2015.08.007

Cited by 24 publications

(19 citation statements)

References 11 publications

(12 reference statements)

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“…Under resting conditions, the frequency of the glutamatergic EPSCs recorded from pyramidal neurons in the hippocampal samples of HS patients were higher compared to the non-seizure controls 12 . Here, we showed that the magnitude of increase in the glutamatergic transmission in the ATL samples was significantly higher than that in the case of the hippocampal samples under resting conditions (Figs 2 and 4).…”

Section: Discussionmentioning

confidence: 78%

“…Previously, we showed that under resting conditions, spontaneous EPSCs on pyramidal neurons were higher in resected hippocampal samples obtained from patients with HS 12 , suggesting a glutamatergic network reorganization in the hippocampus. However, it is not known if the extent of change in excitatory synaptic transmission is similar in the extra-hippocampal regions of patients with HS.…”

Section: Introductionmentioning

confidence: 84%

“…Endogenous NMDA receptor activity plays a crucial role in the generation of enhanced excitatory activity in the hippocampal samples obtained from patients with HS 12 . Using RNA-seq analysis of the hippocampal tissue resected from patients with HS, we have previously identified hubs of genes linked to synaptic transmission and neuronal network modulation 18 .…”

Section: Discussionmentioning

confidence: 99%

“…However, it is not known if the extent of change in excitatory synaptic transmission is similar in the extra-hippocampal regions of patients with HS. We have earlier reported that under resting conditions, endogenous NMDA receptor activity was enhanced in the hippocampal samples obtained from patients with HS 12 . The differential role of NR2A and NR2B subunits carrying NMDA receptors in epileptogenesis has also been reported in animal models of HS 13–16 , suggesting increased excitability due to altered properties of NMDA receptor subunits.…”

Section: Introductionmentioning

confidence: 88%

“…ACSF consisted of CaCl 2 , 2 mM; NaHCO 3 , 25 mM; NaH 2 PO 4 , 1.25 mM; NaCl, 125 mM; KCL, 2.5 mM; MgCl 2 , 1 mM; and Glucose, 25 mM. Samples were further processed for cellular electrophysiological experiments as per the protocol reported earlier 12 . Briefly, samples were placed in well carbogenated, ice-cold ACSF within 2 minutes of resection.…”

Section: Methodsmentioning

confidence: 99%

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Altered glutamatergic tone reveals two distinct resting state networks at the cellular level in hippocampal sclerosis

Banerjee

BanerjeeDixit

Srivastava

et al. 2017

Sci Rep

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Hippocampal sclerosis (HS), the most common subset of drug-resistant epilepsy (DRE), is associated with large-scale network abnormalities, even under resting state. We studied the excitatory postsynaptic currents (EPSCs) recorded from pyramidal neurons in resected samples under resting conditions from the hippocampal and anterior temporal lobe (ATL) obtained from patients with HS (n = 14) undergoing resective surgery. We observed higher frequency and amplitude of spontaneous EPSCs in both the samples compared to non-seizure control samples. Application of tetrodotoxin (TTX) reduced the frequency of spontaneous EPSCs by 49.6 ± 4.3% and 61.8 ± 6.2% in the hippocampal and ATL samples, respectively. The magnitude of reduction caused by TTX with respect to non-seizure controls was significantly higher in the ATL samples than in the hippocampal samples. The magnitude of the change in the expression of the NR2A subunit of the NMDA receptors also varied in these two regions. Thus, the mechanism of hyperexcitabilty mediated by glutamatergic network reorganization in the hippocampal region is different from that in the ATL region of patients with HS, suggesting two independent resting-state networks at the cellular level. Taken together, these findings will improve the understanding of the broadly distributed resting-state networks in HS.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 84%