NERVE GAS-INDUCED SEIZURES - ROLE OF ACETYLCHOLINE IN THE RAPID INDUCTION OF FOS AND GLIAL FIBRILLARY ACIDIC PROTEIN IN PIRIFORM CORTEX

Soman (pinacolymethylphosphonofluoridate), a highly potent irreversibl e inhibitor of acetylcholinesterase (AChE), causes seizures and rapidl y increases Fos and glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This suggests that the inhibition of AChE by so man leads to increased acetylcholine (ACh) and neuronal excitability i n PC. The sole source of cholinergic input to PC is from the nucleus o f the diagonal band (NDB). To investigate the role of ACh in soman-ind uced seizures, we lesioned cholinergic neurons in NDB unilaterally wit h 192-lgG-saporin. By 10 d, saporin eliminated staining for choline ac etyltransferase (ChAT), the synthetic enzyme for ACh, in NDB ipsilater al to the lesion. Staining for AChE, the degradative enzyme for ACh, w as eliminated in PC ipsilateral to the lesioned NDB. By 45-60 min afte r soman, increased Fos and GFAP staining in PC was evident only ipsila teral to the unlesioned NDB. By 90-120 min after soman, Fos and GFAP s taining increased bilaterally in PC. In a second experiment, electrica l stimulation electrodes were implanted unilaterally in the NDB to act ivate focally the projections to PC in unanesthetized rats. Within 5 m in of NDB stimulation, there were clear behavioral and EEG signs of co nvulsions. After 45-60 min of NDB stimulation, there was increased Fos and GFAP staining in layer II of PC ipsilateral to the stimulation si te. Pretreatment with the selective muscarinic receptor antagonist sco polamine blocked the convulsions and prevented increased Fos and GFAP staining in PC. These results suggest that ACh release in PC triggers the initiation of seizures and gliosis after soman administration, pre dominantly by the activation of muscarinic receptors.