Abstract
The medial septal nucleus is one of the basal forebrain nuclei that projects cholinergic input to the hippocampus and cortex. Two of the hallmarks of Alzheimer’s disease (AD) are a significant loss of cholinergic transmission and neuroinflammation, and it has been suggested that these two hallmarks are causally linked to the medial septum. Therefore, we have investigated the age-related susceptibility of medial septal cholinergic neurons to glial activation, mediated via peripheral administration of lipopolysaccharide (500 μg/kg) into ChAT(BAC)-eGFP mice at different ages (3–22 months). Our results show that during normal aging, cholinergic neurons experience a bi-phasic excitability profile, in which increased excitability at adulthood (ages ranging between 9 and 12 months) decreases in aged animals (> 18 months). Moreover, activation of glia had a differential impact on mice from different age groups, affecting K+ conductances in young and adult animals, without affecting aged mice. These findings provide a potential explanation for the increased vulnerability of cholinergic neurons to neuroinflammation with aging as reported previously, thus providing a link to the impact of acute neuroinflammation in AD.
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This work was supported by seed funding grant (WSU) and Ainsworth Medical Research Innovation Fund to Y.B and E.G. O.K is supported by WSU postgraduate scholarship (UWSPRA).
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Kékesi, O., Liang, H., Münch, G. et al. The differential impact of acute microglia activation on the excitability of cholinergic neurons in the mouse medial septum. Brain Struct Funct 224, 2297–2309 (2019). https://doi.org/10.1007/s00429-019-01905-w
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DOI: https://doi.org/10.1007/s00429-019-01905-w