title: N-methyl-D-aspartate-induced oscillatory properties in neocortical pyramidal neurons from patients with epilepsy.
abstract: N-Methyl-D-aspartate (NMDA) receptors have been implicated in epileptogenesis, but how these receptors contribute to epilepsy remains unknown. In particular, their role is likely to be complicated because of their voltage-dependent behavior. Here, the authors investigate how activation of NMDA receptors can affect the intrinsic production of oscillation and the resonance properties of neocortical pyramidal neurons from children with intractable epilepsy. Intracellular whole-cell patch clamp recordings in cortical slices from these patients revealed that pyramidal neurons do not produce spontaneous oscillation under control conditions. However, they did exhibit resonance around 1.5 Hz. On NMDA receptor activation, with bath-applied NMDA (10 μM), the majority of neurons produced voltage-dependent intrinsic oscillation associated with a change in the stability of the neuronal system as reflected by the whole-cell I-V curve. Furthermore, the degree of resonance was amplified while the frequency of resonance was shifted to lower frequencies (∼1 Hz) in NMDA. These results suggest that NMDA receptors may both promote the production of low-frequency oscillation and sharpen the response of the cell to lower frequencies. Both these behaviors may be amplified in tissue from patients with epilepsy, resulting in an increased propensity to generate seizures.
authors.affiliation: Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA. martella@uchicago.edu
authors.forename: Amber
authors.initials: A
authors.lastname: Martell
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dwyer
authors.forename: Henner
authors.initials: H
authors.lastname: Koch
authors.forename: Sebastien
authors.initials: S
authors.lastname: Zanella
authors.forename: Michael
authors.initials: M
authors.lastname: Kohrman
authors.forename: David
authors.initials: D
authors.lastname: Frim
authors.forename: Jan-Marino
authors.initials: JM
authors.lastname: Ramirez
authors.forename: Wim
authors.initials: W
authors.lastname: van Drongelen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000779:Anesthetics, Local / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects*; D001703:Biophysics; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004827:Epilepsy / Q000473:pathology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D019579:Neocortex / Q000473:pathology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D018690:Excitatory Amino Acid Agonists; D013779:Tetrodotoxin; D016202:N-Methylaspartate