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  • 标题:Combined Optogenetic Approaches Reveal Quantitative Dynamics of Endogenous Noradrenergic Transmission in the Brain
  • 本地全文:下载
  • 作者:Shinobu Nomura ; Ludovic Tricoire ; Ivan Cohen
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2020
  • 卷号:23
  • 期号:11
  • 页码:1-27
  • DOI:10.1016/j.isci.2020.101710
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryLittle is known about the real-time cellular dynamics triggered by endogenous catecholamine release despite their importance in brain functions. To address this issue, we expressed channelrhodopsin in locus coeruleus neurons and protein kinase-A activity biosensors in cortical pyramidal neurons and combined two-photon imaging of biosensors with photostimulation of locus coeruleus cortical axons, in acute slices andin vivo. Burst photostimulation of axons for 5–10 s elicited robust, minutes-lasting kinase-A activation in individual neurons, indicating that a single burst firing episode of synchronized locus coeruleus neurons has rapid and lasting effects on cortical network. Responses were mediated by β1 adrenoceptors, dampened by co-activation of α2 adrenoceptors, and dramatically increased upon inhibition of noradrenaline reuptake transporter. Dopamine receptors were not involved, showing that kinase-A activation was due to noradrenaline release. Our study shows that noradrenergic transmission can be characterized with high spatiotemporal resolution in brain slices andin vivousing optogenetic tools.Graphical AbstractDisplay OmittedHighlights•We report all-optogenetic stimulation and imaging of NA transmission in cortex•NA fiber stimulation elicits robust PKA activation in neurons, in slice andin vivo•PKA activation involves both β1 and α2 adrenoceptors but not dopamine receptors•Noradrenaline reuptake transporter activity greatly limits response intensityOptical Imaging; Neuroscience; Cell Biology
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