Abstract
Early Life Inflammation Increases CA1 Pyramidal Neuron Excitability in a Sex and
Age-Dependent Manner Through a Chloride Homeostasis Disruption
Gomez CD, Read J, Acharjee S, Pittman QJ.
J Neurosci
.
2019;39(37):7244.
Early life, systemic inflammation causes long-lasting changes in behavior. To unmask
possible mechanisms associated with this phenomenon, we asked whether the intrinsic
membrane properties in hippocampal neurons were altered as a consequence of early life
inflammation. C57BL/6 mice were bred in-house and both male and female pups from
multiple litters were injected with lipopolysaccharide (LPS; 100 g/kg,
intraperitoneally.) or vehicle at postnatal day (P)14, and kept until adolescence
(P35-P45) or adulthood (P60-P70), when brain slices were prepared for whole-cell and
perforated-patch recordings from CA1 hippocampal pyramidal neurons. In neurons of
adult male mice pretreated with LPS, the number of action potentials elicited by
depolarizing current pulses was significantly increased compared with control neurons,
concomitant with increased input resistance, and a lower action potential threshold.
Although these changes were not associated with changes in relevant sodium channel
expression or differences in capacitance or dendritic architecture, they were linked
to a mechanism involving intracellular chloride overload, revealed through a
depolarized γ aminobutyric acid reversal potential and increased expression of the
chloride transporter, NKCC1. In contrast, no significant changes were observed in
neurons of adult female mice pretreated with LPS, nor in adolescent mice of either
sex. These data uncover a potential mechanism involving neonatal inflammation induced
plasticity in chloride homeostasis, which may contribute to early life
inflammation-induced behavioral alterations.
