Ultrastructural features and synaptic connections of hilar ectopic granule cells in the rat dentate gyrus are different from those of granule cells in the granule cell layer

Abstract

Several investigators have shown the existence of dentate granule cells in ectopic locations within the hilus and molecular layer using both Golgi and retrograde tracing studies but the ultrastructural features and synaptic connections of ectopic granule cells were not previously examined. In the present study, the biocytin retrograde tracing technique was used to label ectopic granule cells following injections into stratum lucidum of CA3b of hippocampal slices obtained from epileptic rats. Electron microscopy was used to study hilar ectopic granule cells that were located 20-40 microm from the granule cell layer (GCL). They had ultrastructural features similar to those of granule cells in the GCL but showed differences, including nuclei that often displayed infoldings and thicker apical dendrites. At their origin, these dendrites were 6 microm in diameter and they tapered down to 2 microm at the border with the GCL. Both biocytin-labeled and unlabeled axon terminals formed exclusively asymmetric synapses with the somata and proximal dendrites of hilar ectopic granule cells. The mean number of axosomatic synapses for these cells was three times that for granule cells in the GCL. Together, these data indicate that hilar ectopic granule cells are postsynaptic to mossy fibers and have less inhibitory input on their somata and proximal dendrites than granule cells in the GCL. This finding is consistent with recent physiological results showing that hilar ectopic granule cells from epileptic rats are more hyperexcitable than granule cells in the GCL.

The Developmental Stage of Dentate Granule Cells Dictates Their Contribution to Seizure-Induced Plasticity

“…In addition to neuronal loss and gliosis, human and experimental mTLE pathology involves prominent dentate granule cell (DGC) abnormalities, including mossy fiber sprouting (MFS), DGCs with abnormal dendrites, and dispersed or ectopically located DGCs (Tauck and Nadler, 1985;de Lanerolle et al, 1989;Houser et al, 1990;Mello et al, 1993;Parent et al, 1997;Spigelman et al, 1998;Buckmaster and Dudek, 1999;Ribak et al, 2000;Scharfman et al, 2000;Dashtipour et al, 2001). DGC abnormalities are associated with network hyperconnectivity that may impact mTLE pathogenesis.…”

“…Hilar ectopic DGCs also arise after SE (Parent et al, 1997). These cells aberrantly integrate into the local circuitry, receive excess excitatory input, exhibit abnormal bursting, and are recruited during spontaneous seizures (Scharfman et al, 2000(Scharfman et al, , 2002Dashtipour et al, 2001).…”

Pilocarpine-Induced Seizures Cause Selective Time-Dependent Changes to Adult-Generated Hippocampal Dentate Granule Cells

“…Similarly, ectopic granule cells, found in the dentate hilus of epileptic brains (Houser, 1990), receive inappropriate innervation and may also contribute to network destabilization (Scharfman et al, 2000;Pierce et al, 2005). Basal dendrites in epileptic animals are found most frequently on granule cells that, based on their migration pattern, are predicted to be newborn (Ribak et al, 2000;Dashtipour et al, 2001Dashtipour et al, , 2002Danzer et al, 2002). Similarly, at least some ectopic granule cells are derived from newborn cells (Jung et al, 2004;Jessberger et al, 2005;Parent et al, 2006).…”

Reelin Regulates Neuronal Progenitor Migration in Intact and Epileptic Hippocampus

“…Mossy fiber sprouting, DGC layer dispersion, and loss of hilar interneuron subsets occur in the pilocarpine mTLE model (Mello et al, 1993;Obenaus et al, 1993;Mello and Covolan, 1996;Kobayashi and Buckmaster, 2003). Pilocarpineor kainic acid-induced status epilepticus (SE) also markedly stimulates DGC neurogenesis and leads to the appearance of hilar-ectopic granule cells (Bengzon et al, 1997;Parent et al, 1997Parent et al, , 2006Scharfman et al, 2000;Dashtipour et al, 2001). Ectopic DGCs integrate abnormally, are hyperexcitable, and thus may contribute to seizures (Scharfman et al, 2000;Dashtipour et al, 2001).…”