title: Scn2a sodium channel mutation results in hyperexcitability in the hippocampus in vitro.
abstract: OBJECTIVE
  To investigate in vitro, the cellular network activity of the hippocampus in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene.
  
  
  METHODS
  Extacellular recordings were obtained from CA1 and CA3 pyramidal neurons in hippocampal slices prepared from Q54 transgenic and nontransgenic littermates (WT) under physiologic conditions as well as during periods of orthodromic stimulation of the Schaffer collaterals. Cerebral spinal fluid samples were analyzed and cresyl violet histology of the hippocampus was conducted.
  
  
  RESULTS
  Increased spontaneous extracellular activity was found in both CA1 and CA3 regions of Q54 hippocampal slices. Q54 slices also demonstrated significantly greater spontaneous and afterdischarge activity as well as population spike amplitude and duration following tetanic stimulus in comparison to WT slices. Frequency analysis of tetanically stimulated recordings indicated high-frequency components (100 and 200 Hz) unique to Q45 slices. Analysis of cresyl violet histology supports healthy Q54 slices up to 10 weeks, while Q54 cerebral spinal fluid shows elevated osmolarity.
  
  
  CONCLUSIONS
  Evidence for hyperexcitability and increased synaptic efficacy in Q54 mice was found by observing spontaneous activity as well as evoked activity. Response to tetanic stimulation included unique high-frequency oscillations, and resulted in an increased population spike amplitude and duration. Histological assessment shows equivalent neuronal development in both experimental groups. The data support the hypothesis that modified Scn2a channels in Q54 mice result in network hyperexcitability of the hippocampus necessary for the development and maintenance of temporal lobe seizures.
authors.affiliation: Neural Engineering Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Kara Buehrer
authors.initials: KB
authors.lastname: Kile
authors.forename: Nan
authors.initials: N
authors.lastname: Tian
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Durand
mesh_terms: D000818:Animals; D048588:Benzoxazines; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000706:statistics & numerical data; D004573:Electrolytes / Q000134:cerebrospinal fluid; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense / Q000235:genetics*; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009994:Osmolar Concentration; D010078:Oxazines; D017966:Pyramidal Cells / Q000473:pathology / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D048588:Benzoxazines; D004573:Electrolytes; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D010078:Oxazines; C000654500:Scn2a protein, mouse; D015222:Sodium Channels; C028911:cresyl violet