Nerve gas-induced seizures

Role of acetylcholine in the rapid induction of Fos and glial fibrillary acidic protein in piriform cortex

Lee A. Zimmer, Matthew Ennis, Ronald G. Wiley, Michael T. Shipley

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Soman (pinacolymethylphosphonofluoridate), a highly potent irreversible inhibitor of acetylcholinesterase (ACHE), causes seizures and rapidly increases Fos and glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This suggests that the inhibition of AChE by soman leads to increased acetylcholine (ACh) and neuronal excitability in PC. The sole source of cholinergic input to PC is from the nucleus of the diagonal band (NDB). To investigate the role of ACh in soman-induced seizures, we lesioned cholinergic neurons in NDB unilaterally with 192-IgG-saporin. By 10 d, saporin eliminated staining for choline acetyltransferase (CHAT), the synthetic enzyme for ACh, in NDB ipsilateral to the lesion. Staining for AChE, the degradative enzyme for ACh, was eliminated in PC ipsilateral to the lesioned NDB. By 45-60 min after soman, increased Fos and GFAP staining in PC was evident only ipsilateral to the unlesioned NDB. By 90-120 min after soman, Fos and GFAP staining increased bilaterally in PC. In a second experiment, electrical stimulation electrodes were implanted unilaterally in the NDB to activate focally the projections to PC in unanesthetized rats. Within 5 min of NDB stimulation, there were clear behavioral and EEG signs of convulsions. After 45-60 min of NDB stimulation, there was increased Fos and GFAP staining in layer II of PC ipsilateral to the stimulation site. Pretreatment with the selective muscarinic receptor antagonist scopolamine 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, predominantly by the activation of muscarinic receptors.

Original languageEnglish (US)
Pages (from-to)3897-3908
Number of pages12
JournalJournal of Neuroscience
Volume18
Issue number10
StatePublished - May 15 1998
Externally publishedYes

Fingerprint

Glial Fibrillary Acidic Protein
Septal Nuclei
Acetylcholine
Soman
Seizures
Staining and Labeling
Muscarinic Receptors
Nerve Agents
Piriform Cortex
Implanted Electrodes
Cholinergic Neurons
Muscarinic Antagonists
Gliosis
Scopolamine Hydrobromide
Choline O-Acetyltransferase
Cholinesterase Inhibitors
Enzymes
Cholinergic Agents
Electric Stimulation
Electroencephalography

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Nerve gas-induced seizures : Role of acetylcholine in the rapid induction of Fos and glial fibrillary acidic protein in piriform cortex. / Zimmer, Lee A.; Ennis, Matthew; Wiley, Ronald G.; Shipley, Michael T.

In: Journal of Neuroscience, Vol. 18, No. 10, 15.05.1998, p. 3897-3908.

Research output: Contribution to journalArticle

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