Combined role of seizure-induced dendritic morphology alterations and spine loss in newborn granule cells with mossy fiber sprouting on the hyperexcitability of a computer model of the dentate gyrus

PLoS Comput Biol. 2014 May 8;10(5):e1003601. doi: 10.1371/journal.pcbi.1003601. eCollection 2014 May.


Temporal lobe epilepsy strongly affects hippocampal dentate gyrus granule cells morphology. These cells exhibit seizure-induced anatomical alterations including mossy fiber sprouting, changes in the apical and basal dendritic tree and suffer substantial dendritic spine loss. The effect of some of these changes on the hyperexcitability of the dentate gyrus has been widely studied. For example, mossy fiber sprouting increases the excitability of the circuit while dendritic spine loss may have the opposite effect. However, the effect of the interplay of these different morphological alterations on the hyperexcitability of the dentate gyrus is still unknown. Here we adapted an existing computational model of the dentate gyrus by replacing the reduced granule cell models with morphologically detailed models coming from three-dimensional reconstructions of mature cells. The model simulates a network with 10% of the mossy fiber sprouting observed in the pilocarpine (PILO) model of epilepsy. Different fractions of the mature granule cell models were replaced by morphologically reconstructed models of newborn dentate granule cells from animals with PILO-induced Status Epilepticus, which have apical dendritic alterations and spine loss, and control animals, which do not have these alterations. This complex arrangement of cells and processes allowed us to study the combined effect of mossy fiber sprouting, altered apical dendritic tree and dendritic spine loss in newborn granule cells on the excitability of the dentate gyrus model. Our simulations suggest that alterations in the apical dendritic tree and dendritic spine loss in newborn granule cells have opposing effects on the excitability of the dentate gyrus after Status Epilepticus. Apical dendritic alterations potentiate the increase of excitability provoked by mossy fiber sprouting while spine loss curtails this increase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cerebellar Nuclei / pathology
  • Cerebellar Nuclei / physiopathology*
  • Computer Simulation
  • Dendritic Spines / pathology*
  • Epilepsy / pathology*
  • Epilepsy / physiopathology*
  • Models, Anatomic
  • Models, Neurological*
  • Nerve Fibers / pathology*
  • Neurogenesis
  • Rats

Grants and funding

JT was the recipient of a Post-Doctoral Fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP, Brazil, grant number (2012/17057-2). NGC is recipient of grants from CNPq, FAPESP, FAPESP-Cinapce, CAPES-PROEX, Brazil. NGC and ACR are also recipients of CNPq-Research Fellowships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.