The environmental neurotoxin trimethyltin (TMT) destroys parts of the hippocampal formation as well as the entorhinal cortex but leaves the septal cholinergic projection to the hippocampus and dentate gyrus intact. In this study we measured choline acetyltransferase (ChAT) activity in micropunch samples of the dentate gyrus, the CA1 region of Ammon's horn, and the caudate-putamen as a measure of density of cholinergic innervation in control rats and rats exposed to 7 mg/kg TMT by means of gastric intubation. Three months after the rats were exposed to a single dose of TMT both the dentate gyrus and CA1 demonstrated significantly higher ChAT activity in TMT-exposed rats than in control rats. No differences were found between groups for the caudate-putamen samples. These results support the hypothesis that exposure to TMT causes reactive synaptogenesis in the cholinergic septohippocampal system.

Trimethyltin (TMT) is known to produce substantial damage to the hippocampal formation. It also destroys neurons within the entorhinal cortex, thereby causing degeneration of perforant path afferents that terminate in the outer molecular layer (OML) of the dentate gyrus. Surgical destruction of the entorhinal cortex also causes the perforant path to degenerate. This leads to reactive synpatogenesis (axonal sprouting) of septal afferents to the dentate gyrus. The purpose of the present study was to determine whether administration of 6 mg/kg of TMT by gavage to rats would cause axonal sprouting within the septodentate projection. A histochemical stain for acetycholinesterase (AChE) was used. Compared to control subjects rats given TMT exhibited significantly denser AChE staining in the dentate OML. This is putative indication of reactive synaptogenesis within the cholinergic projection to this layer of the dentate and is somewhat surprising because other neurotoxins, such as lead and ethanol, that affect neurons within the hippocampal formation reduce the capacity for reactive synaptogenesis in response to lesions of the entorhinal cortex.