title: Enhanced endogenous activation of NMDA receptors in pyramidal neurons of hippocampal tissues from patients with mesial temporal lobe epilepsy: A mechanism of hyper excitation.
abstract: Altered excitatory synaptic transmission is one of the primary causes of seizure generation in patients with mesial temporal lobe epilepsy (MTLE). The present study is designed to delineate the contribution of glutamatergic tone under resting conditions to the hyper excitability in patients with MTLE. Resected hippocampal tissues were obtained from patients with MTLE. In these samples spontaneous excitatory postsynaptic currents (EPSCs), sensitive to NMDA receptor antagonist APV (50μM) and AMPA receptor antagonist CNQX (10μM) were recorded from pyramidal neurons at -70mV. We observed that frequency of EPSCs were 28.2% higher in slices obtained from patients with MTLE compared to that in case of non-epileptic controls. We also examined spontaneous fast current transients (CTs) recorded from these pyramidal neurons under cell-attached configuration. The frequency of CTs increased in the absence of extracellular Mg(2+) in brain slice preparations and was completely blocked by APV. We found that the frequency of CTs in pyramidal neurons were higher in case of MTLE samples compared to non-epileptic controls. This study suggests that enhanced endogenous activity of NMDA receptor contributes to excitability in pyramidal neurons of slice preparations obtained from patients with MTLE.
authors: Center of Excellence for Epilepsy, National Brain Research Center, Manesar, India. Electronic address: jyotirmoybanerjee1@gmail.com.
authors: Jyotirmoy
authors: J
authors: Banerjee
authors: Center of Excellence for Epilepsy, National Brain Research Center, Manesar, India. Electronic address: aparnabanerjeedixit@gmail.com.
authors: Aparna
authors: A
authors: Banerjee Dixit
authors: Center of Excellence for Epilepsy, National Brain Research Center, Manesar, India; Department of Neurology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: manjari.tripathi1@gmail.com.
authors: Manjari
authors: M
authors: Tripathi
authors: Department of Neuropathology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: sarkar.chitra@gmail.com.
authors: Chitra
authors: C
authors: Sarkar
authors: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: yk.ykgupta@gmail.com.
authors: Yogendra Kumar
authors: YK
authors: Gupta
authors: Center of Excellence for Epilepsy, National Brain Research Center, Manesar, India; Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India. Electronic address: saratpchandra3@gmail.com.
authors: P Sarat
authors: PS
authors: Chandra
mesh_terms: D000818:Animals; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Current transients; Excitatory postsynaptic current (EPSC); Glutamate; Mesial temporal lobe epilepsy (MTLE); NMDA receptors