Single mossy fiber axonal systems of human dentate granule cells studied in hippocampal slices from patients with temporal lobe epilepsy [published erratum appears in J Neurosci 1993 Jun;13(6):following table of contents]

Abstract

Previous histological and immunocytochemical studies suggest that reorganization of the dentate granule cell axons, the mossy fibers, can occur in epileptic human hippocampus (Sutula et al., 1989; Houser et al., 1990; Babb et al., 1991) and in animal models of epilepsy (Tauck and Nadler, 1985; Sutula et al., 1988; Cronin et al., 1992). However, neuroanatomical analyses of the trajectory and morphology of reorganized axons are not yet available. The present study was conducted to investigate single dentate granule cell axonal systems in human epileptic hippocampus. Individual mossy fibers were directly visualized by injecting a tracer (biocytin or Lucifer yellow) intracellularly in hippocampal slices prepared from temporal lobes that were surgically removed from patients for treatment of intractable epilepsy. Two major arborization patterns were identified: (1) the parent axons extended to and coursed through the hilus toward CA3, leaving collaterals along their paths in the hilus (N = 19 neurons); (2) in addition to the aforementioned axonal system, collateral(s) branched from the parent axon near the soma and projected to the granule cell layer and molecular layer, forming an aberrant axonal pathway (N = 9 neurons). These aberrant collaterals bore large boutons similar to those of the hilar axons and formed extensive plexuses in the granule cell layer and/or in the molecular layer. The summed length of collaterals in the granular/molecular layers was 1110.8 microns on average, which was one-fourth of the total summed length of the mossy fibers (3698.5 microns on average). The size of the somata in neurons that had aberrant collaterals was significantly larger than that of neurons without such collaterals (p < 0.025). In four cases, filopodium-like fine processes were present near the axon hillock and proximal parts of the parent axon, suggesting that the aberrant collateral formation might be an ongoing process in these tissues. The lack of control slices from normal living human hippocampus makes it difficult to assess to what extent the present findings are epilepsy associated. However, the presence of aberrant mossy fiber collaterals in the hippocampi used in the present study has been confirmed by Timm's staining and/or dynorphin immunohistochemistry in comparison with nonepileptic autopsy material, indicating its relation to epilepsy (Babb et al., 1991, 1992). At present, there seems to be a consensus that the projection of mossy fiber collaterals to the supragranular layer is a rare occurrence in normal rats (Lorento de Nó, 1934; Claiborne et al., 1986; Seress et al., 1991; present study), normal monkeys (Seress et al., 1991), and normal humans (Houser et al., 1990).(ABSTRACT TRUNCATED AT 400 WORDS)

Stimulus and Potassium-Induced Epileptiform Activity in the Human Dentate Gyrus from Patients with and without Hippocampal Sclerosis

“…We found a high coherence of Timm scores 2 and 3 and presence of fluorescent mossy fibers, indicating that the Timm staining provides evidence for aberrant MF sprouting. This is in line with a previous report showing coincidence of intracellularly labeled aberrant mossy fiber arborization and positive staining for zinc or dynorphin in the inner molecular layer (Isokawa et al, 1993). However, the fluorescent-labeled axons in the inner molecular layer may also identify GABAergic or peptidergic axonal systems, involved in reorganization (de Lanerolle et al, 1989(de Lanerolle et al, , 2003Furtinger et al, 2001;Wittner et al, 2001).…”

“…Morphological investigation of the resected tissue revealed that one group of TLEs is associated with hippocampal sclerosis (HS) characterized by segmental or total cell loss, whereas another group shows less segmental cell loss (non-HS) (Babb et al, 1984;Kim et al, 1990;Mathern et al, 1997a). In specimens with HS, the axons of granule cells [mossy fibers (MF)] send collaterals into the dentate inner molecular layer (IML) (Scheibel et al, 1974;Sutula et al, 1989;Houser et al, 1990;Masukawa et al, 1992;Isokawa et al, 1993) and form multiple asymmetric synapses with dendritic structures of granule cells (Babb et al, 1991;Franck et al, 1995;Zhang and Houser, 1999). This rearrangement is associated with increased immunoreactivity for glutamate receptors in the IML (Babb et al, 1996;Ying et al, 1998), suggesting that a recurrent excitatory network of granule cells might be present in sclerotic tissue.…”

Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey

“…Third, N-methyl-D-aspartate and GABA receptor-mediated inputs to CA3 pyramidal cells occur in s. radiatum and oriens, with strong GABA A inhibition associated with somatically localized receptors (42,44,45). Further, in various forms of hippocampal pathology (e.g., mesial temporal sclerosis associated with temporal lobe epilepsy), there is a sprouting of zinc-rich MFs back on to the granule cells of origin (18,20,46,47). Their aberrant terminal localization and their proximity to GABA receptors have prompted investigators to postulate a role for zinc in the breakdown of inhibition that is associated with seizure generation in epileptic hippocampus (48).…”

Effects of chronic network hyperexcitability on the growth of hippocampal dendrites

“…Dendritic abnormalities are also associated with developmental brain disorders (Purpura et al, 1982;Armstrong, 2005;Dierssen and Ramakers, 2006). This is true in epilepsy where a loss of dendritic branches and spines are commonly observed (Ward, 1969;Belichencko et al, 1992;Isokawa et al, 1993;Multani et al, 1994). Both glutamatergic and GABAergic synaptic transmission have been proposed to play important roles in regulating dendritic growth (Barbin et al, 1993;Rajan and Cline, 1998;Sin et al, 2002;Wayman et al, 2006).…”