Morphological Alterations in Newly Born Dentate Gyrus Granule Cells That Emerge after Status Epilepticus Contribute to Make Them Less Excitable

Computer simulations of external current stimulations of dentate gyrus granule cells of rats with Status Epilepticus induced by pilocarpine and control rats were used to evaluate whether morphological differences alone between these cells have an impact on their electrophysiological behavior. The cell models were constructed using morphological information from tridimensional reconstructions with Neurolucida software. To evaluate the effect of morphology differences alone, ion channel conductances, densities and distributions over the dendritic trees of dentate gyrus granule cells were the same for all models. External simulated currents were injected in randomly chosen dendrites belonging to one of three different areas of dentate gyrus granule cell molecular layer: inner molecular layer, medial molecular layer and outer molecular layer. Somatic membrane potentials were recorded to determine firing frequencies and inter-spike intervals. The results show that morphologically altered granule cells from pilocarpine-induced epileptic rats are less excitable than control cells, especially when they are stimulated in the inner molecular layer, which is the target area for mossy fibers that sprout after pilocarpine-induced cell degeneration. This suggests that morphological alterations may act as a protective mechanism to allow dentate gyrus granule cells to cope with the increase of stimulation caused by mossy fiber sprouting.

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico National Counsel of Technological and Scientific Development (CNPq) Brazil

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - "National Counsel of Technological and Scientific Development" (CNPq) -Brazil [156597/2101-1]

CNPq Fellowship

CNPq Fellowship

CNPq

CNPq

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Foundation for Research Support of the State of Sao Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - "Foundation for Research Support of the State of Sao Paulo" (FAPESP)

Cooperacao Interinstitucional de Apoio a Pesquisas sobre o Cerebro da FAPESP Interinstitutional Cooperation in Support of Brain Research Program of FAPESP (FAPESPCinapce)

Cooperacao Interinstitucional de Apoio a Pesquisas sobre o Cerebro da FAPESP "Inter-institutional Cooperation in Support of Brain Research Program of FAPESP" (FAPESP-Cinapce)

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior Federal Agency of Support and Evaluation of Postgraduate Education (CAPES)

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - "Federal Agency of Support and Evaluation of Postgraduate Education" (CAPES)

CAPES program of Academic Excellence (CAPES-PROEX), Brazil

CAPES program of Academic Excellence (CAPESPROEX), Brazil