Selective reduction in ventral hippocampal acetylcholine release in awake galanin-treated rats and galanin-overexpressing transgenic mice

Abstract

The neuropeptide galanin is an inhibitory modulator of hippocampal acetylcholine (ACh) release and cognitive functions. Anatomical evidence demonstrated some differences between the dorsal and ventral hippocampi notably in the expression of galanin receptor subtypes, and the neuronal population on which galanin-like immunoreactivity is expressed. This is suggestive of a differential role for this peptide in these two areas of the hippocampal formation. Using in vivo microdialysis, we investigated the role of galanin on ACh release in the dorsal and ventral hippocampi. Two models were studied: galanin-administered rats and transgenic mice over-expressing galanin (GAL-tg). In rats, galanin (2.0 and 10.0 μM) infused locally through the dialysis probe induced a significant decrease in ACh release in the ventral hippocampus, confirming previous findings, while no effect was seen in the dorsal hippocampus. Using the no net flux method, a significant reduction in ACh levels was noted only in the ventral hippocampus of GAL-tg compared to wild-type littermates. These results suggest that excess endogenous galanin can suppress basal ACh release, with anatomical specificity, to the ventral hippocampus. These results are of interest in the context of galanin receptor subtypes in the dorsal and ventral hippocampus, and the differential alterations of hippocampal subregions in neurological diseases such as Alzheimer's dementia.