TY - JOUR
T1 - The differential impact of acute microglia activation on the excitability of cholinergic neurons in the mouse medial septum
AU - Kékesi, Orsolya
AU - Liang, Huazheng
AU - Münch, Gerald
AU - Morley, John W.
AU - Gyengesi, Erika
AU - Buskila, Yossi
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
KW - Aging
KW - Calcium homeostasis
KW - Cholinergic neurons
KW - Medial septum
KW - Neuroinflammation
UR - http://www.scopus.com/inward/record.url?scp=85067788074&partnerID=8YFLogxK
U2 - 10.1007/s00429-019-01905-w
DO - 10.1007/s00429-019-01905-w
M3 - Article
C2 - 31197438
AN - SCOPUS:85067788074
SN - 1863-2653
VL - 224
SP - 2297
EP - 2309
JO - Brain Structure and Function
JF - Brain Structure and Function
IS - 7
ER -