Spatial exploration induced expression of immediate early genes Fos and Zif268 in adult-born neurons Is reduced after pentylenetetrazole kindling

•PTZ kindling results in similar changes in exploratory behaviour.•PTZ kindling decreased the number of Fos + and Zif268+ cells in the dentate gyrus after exploration.•PTZ kindling decreased the number of 2.5-week old BrdU + cells expressing Fos or Zif268 after exploration.•Behavioural-induced Zif26...

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Veröffentlicht in:Brain research bulletin 2019-10, Vol.152, p.74-84
Hauptverfasser: Kalinina, Alena, Maletta, Teresa, Carr, Joshua, Lehmann, Hugo, Fournier, Neil M.
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Sprache:eng
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Zusammenfassung:•PTZ kindling results in similar changes in exploratory behaviour.•PTZ kindling decreased the number of Fos + and Zif268+ cells in the dentate gyrus after exploration.•PTZ kindling decreased the number of 2.5-week old BrdU + cells expressing Fos or Zif268 after exploration.•Behavioural-induced Zif268 in immature dentate granule cells was reduced after PTZ kindling. Seizure activity stimulates adult neurogenesis, the birth of new neurons, in the hippocampus. Many new neurons that develop in the presence of repeatedly induced seizures acquire abnormal morphological and functional characteristics that can promote network hyperexcitability and hippocampal dysfunction. However, the impact of seizure induced neurogenesis on behaviour remains poorly understood. In this study, we investigated whether adult-born neurons generated immediately before and during chronic seizures were capable of integration into behaviorally relevant hippocampal networks. Adult rats underwent pentylenetetrazole (PTZ) kindling for either 1 or 2 weeks. Proliferating cells were labelled with BrdU immediately before kindling commenced. Twenty-four hours after receiving their last kindling treatment, rats were placed in a novel environment and allowed to freely explore for 30 min. The rats were euthanized 90 min later to examine for behaviourally-induced immediate early gene expression (c-fos, Zif268). Using this approach, we found that PTZ kindled rats did not differ from control rats in regards to exploratory behaviour, but there was a marked attenuation in behaviour-induced expression of Fos and Zif268 for rats that received 2 weeks of PTZ kindling. Further examination revealed that PTZ kindled rats showed reduced colocalization of Fos and Zif268 in 2.5 week old BrdU + cells. The proportion of immature granule cells (doublecortin-positive) expressing behaviorally induced Zif268 was also significantly lower for PTZ kindled rats than control rats. These results suggest that chronic seizures can potentially disrupt the ability of adult-born cells to functionally integrate into hippocampal circuits important for the processing of spatial information.
ISSN:0361-9230
1873-2747
DOI:10.1016/j.brainresbull.2019.07.003