title: Orthogonal wave propagation of epileptiform activity in the planar mouse hippocampus in vitro.
abstract: OBJECTIVE
  In vitro brain preparations have been used extensively to study the generation and propagation of epileptiform activity. Transverse and longitudinal slices of the rodent hippocampus have revealed various patterns of propagation. Yet intact connections between the transverse and longitudinal pathways should generate orthogonal (both transverse and longitudinal) propagation of seizures involving the entire hippocampus. This study utilizes the planar unfolded mouse hippocampus preparation to reveal simultaneous orthogonal epileptiform propagation and to test a method of arresting propagation.
  
  
  METHODS
  This study utilized an unfolded mouse hippocampus preparation. It was chosen due to its preservation of longitudinal neuronal processes, which are thought to play an important role in epileptiform hyperexcitability. 4-Aminopyridine (4-AP), microelectrodes, and voltage-sensitive dye imaging were employed to investigate tissue excitability.
  
  
  RESULTS
  In 50-μm 4-AP, stimulation of the stratum radiatum induced transverse activation of CA3 cells but also induced a longitudinal wave of activity propagating along the CA3 region at a speed of 0.09 m/s. Without stimulation, a wave originated at the temporal CA3 and propagated in a temporal-septal direction could be suppressed with glutamatergic receptor antagonists. Orthogonal propagation traveled longitudinally along the CA3 pathway, secondarily invading the CA1 region at a velocity of 0.22 ± 0.024 m/s. Moreover, a local lesion restricted to the CA3 region could arrest wave propagation.
  
  
  CONCLUSIONS
  These results reveal a complex two-dimensional epileptiform wave propagation pattern in the hippocampus that is generated by a combination of synaptic transmission and axonal propagation in the CA3 recurrent network. Epileptiform propagation block via a transverse selective CA3 lesion suggests a potential surgical technique for the treatment of temporal lobe epilepsy.
authors.affiliation: Neural Engineering Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Kibler
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Durand
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011726:Pyridinium Compounds / Q000378:metabolism; D013997:Time Factors; D056969:Voltage-Sensitive Dye Imaging / Q000379:methods
chemical_list: D011726:Pyridinium Compounds; C054158:RH 414