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. 2008 Oct 8;328(1):69–82. doi: 10.1124/jpet.108.146068

Fig. 13.

Fig. 13.

Scheme illustrating the network effect of soman and galantamine. The pyramidal neuron (P) in the CA1 hippocampal region receives inhibitory inputs from various interneurons. The SRI provides the feed-forward inhibition, whereas both SOI and SPI provide feedback inhibition to the pyramidal neurons. Soman suppresses feedback inhibition (i.e., causes disinhibition) via inhibition of type IA currents in SOI and SPI. Soman enhances feed-forward inhibition via enhancement of ACh-induced type IA currents and via increase in the number of SRI with type II currents. Soman-induced imbalance in feed-forward and feedback inhibition results in increased pyramidal neuron firing leading to excitotoxicity, neuronal damage, and altered rhythm. The loss of pyramidal neurons partly contributes to a decrease in type III nAChR activity after exposure to soman. Galantamine opposes the action of soman by preventing irreversible inhibition of AChE, leading to preservation of nAChR activity, and/or by inducing changes in the expression of nAChRs in the interneurons, thereby restoring the balance of nAChR-dependent feed-forward and feedback inhibition in the hippocampal neurocircuitry.