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

• Published in: Angewandte Chemie International Edition Vol. 61; no. 34; pp. e202206122 - n/a
• Main Authors: Xiong, Hejian, Lacin, Emre, Ouyang, Hui, Naik, Aditi, Xu, Xueqi, Xie, Chen, Youn, Jonghae, Wilson, Blake A., Kumar, Krutin, Kern, Tyler, Aisenberg, Erin, Kircher, Daniel, Li, Xiuying, Zasadzinski, Joseph A., Mateo, Celine, Kleinfeld, David, Hrabetova, Sabina, Slesinger, Paul A., Qin, Zhenpeng
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 22.08.2022
• Edition: International ed. in English
• Subjects: Biological activity; Biosensors; Brain; Central nervous system; Cerebral cortex; Fluorescence; Infrared radiation; Neocortex; Neuropeptide Release; Neuropeptide Transmission; Neuropeptides; Neurotransmitters; Plasmonic Nanovesicles; Signaling; Somatostatin
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202206122

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. An integrated optical approach was developed by combining plasmonic nanovesicles (Au‐nV‐SST) and a cell‐based neurotransmitter fluorescent engineered reporter (CNiFER) for neuropeptide release and detection. This approach allows spatiotemporal mapping of neuropeptide volume transmission and signaling in the mouse cortex.