ANATOMICAL LOCALIZATION AND TIME-COURSE OF FOS EXPRESSION FOLLOWING SOMAN-INDUCED SEIZURES

Soman (pinacolymethylphosphonofluoridate), a highly potent, irreversib le inhibitor of cholinesterase, causes intense convulsions, neuropatho logy and, ultimately, death. There is evidence that certain brain stru ctures are selectively vulnerable to the pathological consequences of soman-induced seizures. A working hypothesis is that central nervous s ystem (CNS) structures with the earliest and most severe signs of neur opathology may be key sites for the initiation of the seizures. Fos, t he immediate-early gene product, increases rapidly in several animal s eizure models. Thus, we reasoned that the earliest brain regions to ex press Fos might be involved in the initiation and maintenance of soman -induced convulsions. To assess this, rats were injected with a single , convulsive dose of soman (77.7 mu g/kg, i.m.). The animals were euth anized and processed for immunocytochemical analysis at several time p oints. Robust Fos expression was seen lm layer II of the piriform cort ex and the noradrenergic nucleus locus coeruleus within 30-45 minutes. One hour following soman injection, staining was more intense in the piriform cortex layer II and in the locus coeruleus. In addition, Fos was evident in the piriform cortex layer III, the entorhinal cortex, t he endopiriform nucleus, the olfactory tubercle, the anterior olfactor y nucleus and the main olfactory bulb. By 2 hours, Fos staining was pr esent throughout the cerebral cortex, thalamus, caudate-putamen and th e hippocampus. At 8 hours and beyond, Fos expression returned to contr ol levels throughout the CNS except for the piriform cortex and the lo cus coeruleus which still had robust labeling. By 24 hours, neuropatho logy was evident throughout the rostral-caudal extent of layer II of t he piriform cortex. The rapid induction of Fos in the piriform cortex and the locus coeruleus, taken together with previous anatomical, elec trophysiological and neurochemical studies, suggests that prolonged, e xcessive exposure to synaptically released acetylcholine and norepinep hrine triggers the production of soman-induced seizures initially in t he piriform cortex and subsequently in other cortical and subcortical structures. (C) 1997 Wiley-Liss, Inc.