期刊
ENEURO
卷 6, 期 6, 页码 -出版社
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0217-19.2019
关键词
fragile X syndrome; ion channels; neurodeveloment; SK channels
资金
- National Centre for Biological Sciences/Tata Institute of Fundamental Research Intramural funds
- Department of Biotechnology
Fragile X syndrome (FXS) is the most common source of intellectual disability and autism. Extensive studies have been performed on the network and behavioral correlates of the syndrome, but our knowledge about intrinsic conductance changes is still limited. In this study, we show a differential effect of FMRP knockout in different subsections of hippocampus using whole-cell patch clamp in mouse hippocampal slices. We observed no significant change in spike numbers in the CA1 region of hippocampus, but a significant increase in CA3, in juvenile mice. However, in adult mice we see a reduction in spike number in the CA1 with no significant difference in CA3. In addition, we see increased variability in spike numbers in CA1 cells following a variety of steady and modulated current step protocols. This effect emerges in adult mice (8 weeks) but not juvenile mice (4 weeks). This increased spiking variability was correlated with reduced spike number and with elevated AHP. The increased AHP arose from elevated SK currents (small conductance calcium-activated potassium channels), but other currents involved in medium AHP, such as I-h and M, were not significantly different. We obtained a partial rescue of the cellular variability phenotype when we blocked SK current using the specific blocker apamin. Our observations provide a single-cell correlate of the network observations of response variability and loss of synchronization, and suggest that the elevation of SK currents in FXS may provide a partial mechanistic explanation for this difference.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据