title: Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures.
abstract: BACKGROUND
  Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg2+-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.
  
  
  RESULTS
  Within 24 hrs of the insult regional specific changes in neuronal firing patterns were evident as: (i) a dramatic reduction in the ability of CA3 to generate firing; and (ii) a contrasting increase in the frequency and duration of synchronized neuronal firing events in CA1. Two distinct processes underlie the increased propensity of CA1 to generate synchronized burst firing; a lack of ability of the CA3 region to 'pace' CA1 resulting in an increased frequency of synchronized events; and a change in the 'intrinsic' properties limited to the CA1 region, which is responsible for increased event duration. Neuronal quantification using NeuN immunoflurescent staining and stereological confocal microscopy revealed no significant cell loss in hippocampal sub regions, suggesting that changes in the properties of neurons within this region were responsible for the KA-mediated excitability changes.
  
  
  CONCLUSIONS
  These results provide novel insight into adaptation of hippocampal circuits following excitotoxic injury. KA-mediated disruption of the interplay between CA3 and CA1 clearly increases the propensity to synchronized firing in CA1.
authors.affiliation: Department of Physiology, The University of Melbourne, Melbourne, Australia. careid@unimelb.edu.au
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reid
authors.forename: Brendan E L
authors.initials: BE
authors.lastname: Adams
authors.forename: Damian
authors.initials: D
authors.lastname: Myers
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology* / Q000633:toxicity; D008564:Membrane Potentials / Q000187:drug effects; D018613:Microscopy, Confocal; D009498:Neurotoxins / Q000494:pharmacology; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000819:agonists / Q000502:physiology
chemical_list: D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D009498:Neurotoxins; D018092:Kainic Acid Receptors