Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question. The 527-cell model, containing granule, mossy, basket, and hilar cells with axonal projections to the perforant-path termination zone, showed that even weak mossy fiber sprouting (10-15% of the strong sprouting observed in the pilocarpine model of epilepsy) resulted in the spread of seizure-like activity to the adjacent model hippocampal laminae after focal stimulation of the perforant path. See reference for more and details.
Model Type: Realistic Network
Region(s) or Organism(s): Dentate gyrus
Cell Type(s): Dentate gyrus granule GLU cell; Dentate gyrus mossy cell; Dentate gyrus basket cell; Dentate gyrus hilar cell
Currents: I L high threshold; I T low threshold; I K; I h; I K,Ca; I Calcium; I Potassium
Model Concept(s): Activity Patterns; Spatio-temporal Activity Patterns; Axonal Action Potentials; Epilepsy; Synaptic Integration
Simulation Environment: NEURON; neuroConstruct (web link to model)
Implementer(s): Santhakumar, Vijayalakshmi [santhavi at umdnj.edu]
References:
Santhakumar V, Aradi I, Soltesz I. (2005). Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: a network model of the dentate gyrus incorporating cell types and axonal topography. Journal of neurophysiology. 93 [PubMed]