Selective loss of dentate hilar interneurons contributes to reduced synaptic inhibition of granule cells in an electrical stimulation-based animal model of temporal lobe epilepsy
Article first published online: 19 DEC 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 500, Issue 5, pages 876–893, 10 February 2007
How to Cite
Sun, C., Mtchedlishvili, Z., Bertram, E. H., Erisir, A. and Kapur, J. (2007), Selective loss of dentate hilar interneurons contributes to reduced synaptic inhibition of granule cells in an electrical stimulation-based animal model of temporal lobe epilepsy. J. Comp. Neurol., 500: 876–893. doi: 10.1002/cne.21207
- Issue published online: 19 DEC 2006
- Article first published online: 19 DEC 2006
- Manuscript Accepted: 7 SEP 2006
- Manuscript Revised: 14 AUG 2006
- Manuscript Received: 22 MAY 2006
- National Institute of Neurological Disorders and Stroke (NINDS). Grant Numbers: RO1 NS40337, RO1NS044370, RO1 NS025605
- neuropeptide Y;
- status epilepticus
Neuropeptide-containing hippocampal interneurons and dentate granule cell inhibition were investigated at different periods following electrical stimulation-induced, self-sustaining status epilepticus (SE) in rats. Immunohistochemistry for somatostatin (SOM), neuropeptide Y (NPY), parvalbumin (PV), cholecystokinin (CCK), and Fluoro-Jade B was performed on sections from hippocampus contralateral to the stimulated side and studied by confocal laser scanning microscopy. Compared to paired age-matched control animals, there were fewer SOM and NPY-immunoreactive (IR) interneurons in the hilus of the dentate gyrus in animals with epilepsy (40–60 days after SE), and 1, 3, and 7 days following SE. In the hilus of animals that had recently undergone SE, some SOM-IR and NPY-IR interneurons also stained for Fluoro-Jade B. Furthermore, there was electron microscopic evidence of the degeneration of SOM-IR interneurons following SE. In contrast, the number of CCK and PV-IR basket cells in epileptic animals was similar to that in controls, although it was transiently diminished following SE; there was no evidence of degeneration of CCK or PV-IR interneurons. Patch-clamp recordings revealed a diminished frequency of inhibitory postsynaptic currents in dentate granule cells (DGCs) recorded from epileptic animals and animals that had recently undergone SE compared with controls. These results confirm the selective vulnerability of a particular subset of dentate hilar interneurons after prolonged SE. This loss may contribute to the reduced GABAergic synaptic inhibition of granule cells in epileptic animals. J. Comp. Neurol. 500:876–893, 2007. © 2006 Wiley-Liss, Inc.