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The differential impact of acute microglia activation on the excitability of cholinergic neurons in the mouse medial septum


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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Correspondence to Yossi Buskila.

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All procedures performed in this study involving animals were in accordance with the ethical standards of Western Sydney University (Animal Research Authority #A11199) at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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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).

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