Granule cell dispersion in temporal lobe epilepsy is associated with changes in dendritic orientation and spine distribution

Granule cell dispersion is a characteristic feature of Ammon's horn sclerosis in temporal lobe epilepsy. It was recently shown that granule cell dispersion is associated with decreased expression of the extracellular matrix protein Reelin. Reelin controls neuronal lamination and the differentiation of dendrites and spines. Here, we studied dendritic orientation and the distribution of dendritic spines on granule cells in surgical specimens of patients suffering from temporal lobe epilepsy. In this material, we compared granule cells in dentate areas showing granule cell dispersion with granule cells in areas exhibiting a normal, densely packed granule cell layer. Granule cells (GC) were Golgi-stained and analyzed using a computer-based camera lucida system and were categorized as being located proximal or distal to the hilus (GCprox, GCdist). We found that GCprox in a densely packed granule cell layer exhibited a mainly vertically oriented dendritic arbor with a small bifurcation angle (17°) between branching dendrites. In contrast, GCdist in a densely packed granular layer showed a wider bifurcation angle (35°), suggesting a widening of the dendritic field during the migratory process to superficial positions. Granule cells in the dispersed granule cell layer showed an even wider bifurcation angle of their apical dendrites (GCprox: 40°; GCdist: 58°) and also exhibited recurrent basal dendrites. Spine density on dendrites of GCprox in dispersed areas was increased compared to GCprox in the normal, compact granule cell layer. In contrast, dendrites of GCdist extending into the molecular layer showed a reduced spine density in dispersed areas. The results are discussed in view of other findings on neuronal reorganization in the epileptic dentate gyrus.

Research highlights
► Decreased expression of the migration-stop protein Reelin in hippocampal sclerosis.
► Granule cell dispersion is associated with decreased Reelin expression.
► Granule cells show spreading of their dendritic trees in dispersion.
► Postsynaptic spine density in the granule cell layer is increased in dispersion.