Probing Neuropeptide Volume Transmission In Vivo by Simultaneous Near-Infrared Light-Triggered Release and Optical Sensing**

Hejian Xiong, Emre Lacin, Hui Ouyang, Aditi Naik, Xueqi Xu, Chen Xie, Jonghae Youn, Blake A. Wilson, Krutin Kumar, Tyler Kern, Erin Aisenberg, Daniel Kircher, Xiuying Li, Joseph A. Zasadzinski, Celine Mateo, David Kleinfeld, Sabina Hrabetova, Paul A. Slesinger, Zhenpeng Qin

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Neuropeptides are abundant signaling molecules in the central nervous system. Yet remarkably little is known about their spatiotemporal spread and biological activity. Here, we developed an integrated optical approach using Plasmonic nAnovesicles and cell-based neurotransmitter fluorescent engineered reporter (CNiFER), or PACE, to probe neuropeptide signaling in the mouse neocortex. Small volumes (fL to pL) of exogenously supplied somatostatin-14 (SST) can be rapidly released under near-infrared light stimulation from nanovesicles implanted in the brain and detected by SST2 CNiFERs with nM sensitivity. Our measurements reveal reduced but synchronized SST transmission within 130 μm, and markedly smaller and delayed transmission at longer distances. These measurements enabled a quantitative estimation of the SST loss rate due to peptide degradation and binding. PACE offers a new tool for determining the spatiotemporal scales of neuropeptide volume transmission and signaling in the brain.

Original languageEnglish (US)
JournalAngewandte Chemie - International Edition
Issue number34
StateAccepted/In press - 2022

Bibliographical note

Funding Information:
We thank Dr. Oliver Griesbeck for providing the Twitch2B cDNA clone and discussions. Schematic figures were made with This work was partially supported by National Science Foundation under award number 1631910 (Z.Q.), National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH) under award number RF1NS110499 (Z.Q., P.A.S.), National Institute of Mental Health of NIH under award number R01MH111499 (P.A.S.), Human Frontier Science Program (HFSP) under award RGP0036/2020 (S.H.), and a postdoc research grant from the Phospholipid Research Center (Heidelberg, Germany) to H.X.

Publisher Copyright:
© 2022 Wiley-VCH GmbH.


  • Biosensors
  • Brain
  • Neuropeptide Release
  • Neuropeptide Transmission
  • Plasmonic Nanovesicles
  • Somatostatin/metabolism
  • Animals
  • Signal Transduction
  • Neuropeptides
  • Mice
  • Brain/metabolism

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Journal Article
  • Research Support, N.I.H., Extramural


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