TY - JOUR
T1 - Ultrafast Glutamate Biosensor Recordings in Brain Slices Reveal Complex Single Exocytosis Transients
AU - Wang, Yuanmo
AU - Mishra, Devesh
AU - Bergman, Jenny
AU - Keighron, Jacqueline D.
AU - Skibicka, Karolina P.
AU - Cans, Ann Sofie
N1 - Funding Information:
*E-mail: cans@chalmers.se. ORCID Ann-Sofie Cans: 0000-0002-3059-2399 Author Contributions This project was conceived and designed by A-S.C, Y.W., J.B., D.M., and K.S., J.D.K took part in the initial development stage of the glutamate sensor concept. Y.W. performed the flocculation assays, DLS and NTA measurements, analyzed and prepared figures of these results. D.M. performed the brain slicing, and Y.W. and D.M performed the ex vivo electrochemical glutamate recordings in brain slices. Y.W. analyzed the ex vivo recording data and prepared figures of these results. J.B. characterized the sensor for selectivity and sensitivity; analyzed and prepared the figures of these results. Y.W. performed the selectivity experiment using cyclic voltammetry, analyzed and prepared a figure of the results. The authors Y.W, J.B and D.M wrote the first draft of this manuscript, K.S and AS.C improved the manuscript further. All authors have read, discussed, and approved the final version of this manuscript. Funding We gratefully acknowledge financial support from The Swedish Research Council, The Swedish Brain Foundation, Ragnar Söderberg Foundation, The Novo Nordisk Foundation, The Wallenberg Center for Molecular and Translational Medicine at the University of Gothenburg, Ernst and Fru Rådman Colliander Stiftelse, Wilhelm and Martina Lundgren Stiftelse, and Magnus Bergvall Stiftelse. Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/3/20
Y1 - 2019/3/20
N2 - Neuronal communication relies on vesicular neurotransmitter release from signaling neurons and detection of these molecules by neighboring neurons. Glutamate, the main excitatory neurotransmitter in the mammalian brain, is involved in nearly all brain functions. However, glutamate has suffered from detection schemes that lack temporal and spatial resolution allowed by electrochemistry. Here we show an amperometric, novel, ultrafast enzyme-based nanoparticle modified sensor, measuring random bursts of hundreds to thousands of rapid spontaneous glutamate exocytotic release events at approximately 30 Hz frequency in the nucleus accumbens of rodent brain slices. Characterizing these single submillisecond exocytosis events revealed a great diversity in spike shape characteristics and size of quantal release, suggesting variability in fusion pore dynamics controlling the glutamate release by cells in this brain region. Hence, this novel biosensor allows recording of rapid single glutamate exocytosis events in the brain tissue and offers insight on regulatory aspects of exocytotic glutamate release, which is critical to understanding of brain glutamate function and dysfunction.
AB - Neuronal communication relies on vesicular neurotransmitter release from signaling neurons and detection of these molecules by neighboring neurons. Glutamate, the main excitatory neurotransmitter in the mammalian brain, is involved in nearly all brain functions. However, glutamate has suffered from detection schemes that lack temporal and spatial resolution allowed by electrochemistry. Here we show an amperometric, novel, ultrafast enzyme-based nanoparticle modified sensor, measuring random bursts of hundreds to thousands of rapid spontaneous glutamate exocytotic release events at approximately 30 Hz frequency in the nucleus accumbens of rodent brain slices. Characterizing these single submillisecond exocytosis events revealed a great diversity in spike shape characteristics and size of quantal release, suggesting variability in fusion pore dynamics controlling the glutamate release by cells in this brain region. Hence, this novel biosensor allows recording of rapid single glutamate exocytosis events in the brain tissue and offers insight on regulatory aspects of exocytotic glutamate release, which is critical to understanding of brain glutamate function and dysfunction.
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U2 - 10.1021/acschemneuro.8b00624
DO - 10.1021/acschemneuro.8b00624
M3 - Article
C2 - 30605606
AN - SCOPUS:85060201028
SN - 1948-7193
VL - 10
SP - 1744
EP - 1752
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 3
ER -