期刊
JOURNAL OF NEUROSCIENCE
卷 39, 期 37, 页码 7244-7259出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2973-18.2019
关键词
GABA reversal potential; hippocampus; inflammation; intrinsic membrane properties; lipopolysaccharide; sex differences
资金
- Natural Sciences and Engineering Research Council of Canada
- Canadian Institutes of Health Research
- CONACyT-the Mexican Council of Science and Technology
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. C57BU6 mice were bred in-house and both male and female pups from multiple litters were injected with lipopolysaccharide (LPS; 100 mu g/kg, i.p.) 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 GABA 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.
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