4.8 Article

Simultaneous two-photon imaging of action potentials and subthreshold inputs in vivo

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27444-9

Keywords

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Funding

  1. National Eye Institute (NEI) [R01EY011787]
  2. National Institute of Neurological Disease and Stroke [R01NS110422, R34NS116740]
  3. National Institute of Mental Health (NIMH) [R01MH100561]
  4. US Army Research Laboratory
  5. US Army Research Office (ARO) [W911NF-12-1-0594]
  6. The Uehara Memorial Foundation
  7. The Japan Society for the Promotion of Science (JSPS) [20K15914]
  8. The Japan Science Society (Sasakawa Scientific Research Grant) [2019-4055]
  9. Hamamatsu Foundation for Science and Technology Promotion
  10. Takeda Science Foundation
  11. Deutsche Forschungsgemeinschaft (DFG) [WE 5517/1-1]
  12. Grants-in-Aid for Scientific Research [20K15914] Funding Source: KAKEN

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The authors introduced a genetically-encoded voltage indicator to measure subthreshold membrane potentials, combined with two-photon imaging to map epileptic seizures progression. The development of ArcLight-ST allows for specific measurement of subthreshold membrane potentials with cellular resolution. The method demonstrated utility in mapping epileptic seizures progression through cortical circuits.
The authors present a geneticallyencoded voltage indicator to specifically measure subthreshold membrane potentials. They combine two-photon imaging of voltage and calcium to map epileptic seizures progression through cortical circuits. To better understand the input-output computations of neuronal populations, we developed ArcLight-ST, a genetically-encoded voltage indicator, to specifically measure subthreshold membrane potentials. We combined two-photon imaging of voltage and calcium, and successfully discriminated subthreshold inputs and spikes with cellular resolution in vivo. We demonstrate the utility of the method by mapping epileptic seizures progression through cortical circuits, revealing divergent sub- and suprathreshold dynamics within compartmentalized epileptic micronetworks. Two-photon, two-color imaging of calcium and voltage enables mapping of inputs and outputs in neuronal populations in living animals.

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