Elsevier

Neuroscience

Volume 104, Issue 3, 14 June 2001, Pages 741-759
Neuroscience

Survival of dentate hilar mossy cells after pilocarpine-induced seizures and their synchronized burst discharges with area CA3 pyramidal cells

https://doi.org/10.1016/S0306-4522(01)00132-4Get rights and content

Abstract

The clinical and basic literature suggest that hilar cells of the dentate gyrus are damaged after seizures, particularly prolonged and repetitive seizures. Of the cell types within the hilus, it appears that the mossy cell is one of the most vulnerable. Nevertheless, hilar neurons which resemble mossy cells appear in some published reports of animal models of epilepsy, and in some cases of human temporal lobe epilepsy. Therefore, mossy cells may not always be killed after severe, repeated seizures. However, mossy cell survival in these studies was not completely clear because the methods did allow discrimination between mossy cells and other hilar cell types. Furthermore, whether surviving mossy cells might have altered physiology after seizures was not examined. Therefore, intracellular recording and intracellular dye injection were used to characterize hilar cells in hippocampal slices from pilocarpine-treated rats that had status epilepticus and recurrent seizures (‘epileptic’ rats). For comparison, mossy cells were also recorded from age-matched, saline-injected controls, and pilocarpine-treated rats that failed to develop status epilepticus.

Numerous hilar cells with the morphology, axon projection, and membrane properties of mossy cells were recorded in all three experimental groups. Thus, mossy cells can survive severe seizures, and those that survive retain many of their normal characteristics. However, mossy cells from epileptic tissue were distinct from mossy cells of control rats in that they generated spontaneous and evoked epileptiform burst discharges. Area CA3 pyramidal cells also exhibited spontaneous and evoked bursts. Simultaneous intracellular recordings from mossy cells and pyramidal cells demonstrated that their burst discharges were synchronized, with pyramidal cell discharges typically beginning first.

From these data we suggest that hilar mossy cells can survive status epilepticus and chronic seizures. The fact that mossy cells have epileptiform bursts, and that they are synchronized with area CA3, suggest a previously unappreciated substrate for hyperexcitability in this animal model.

Section snippets

Experimental procedures

Animal care and use met the guidelines set by the National Institutes of Health and the New York State Department of Health. All efforts were made to minimize the number of animals used and their suffering. All chemicals were purchased from Sigma (St. Louis, MO, USA) unless otherwise noted.

Results

This study is based on 42 mossy cells recorded from 21 animals. Eight were injected with pilocarpine and had status epilepticus followed by recurrent seizures. The number of seizures that were witnessed ranged from three to 42, but this is quite likely to be an underestimate because observations were not made continuously (see Experimental procedures). These rats are referred to below as ‘epileptic’. Slices were made 1–6 months after status, and 20 mossy cells were recorded.

Six rats were

Summary

The results suggest that mossy cells can survive status epilepticus and chronic seizures in rats. The cells that survived had similar morphological and intrinsic electrophysiological properties as mossy cells from saline controls, but had spontaneous and evoked epileptiform discharges. These discharges were synchronized with epileptiform bursts of area CA3 pyramidal cells. Simultaneous intracellular recording showed that the majority of pyramidal cell bursts occurred prior to mossy cell burst

Acknowledgements

We thank Annmarie Curcio and Ruth Marshall for technical and secretarial assistance. This study was supported by NIH Grant 38285 to H.E.S.

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