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Abstract
Understanding the roles of different cell types in the behaviors generated by neural circuits requires protein indicators that report neural activity with high spatio-temporal resolution. Genetically encoded fluorescent protein (FP) voltage sensors, which optically report the electrical activity in distinct cell populations, are, in principle, ideal candidates. Here we demonstrate that the FP voltage sensor ArcLight reports odor-evoked electrical activity in the in vivo mammalian olfactory bulb in single trials using both wide-field and 2-photon imaging. ArcLight resolved fast odorant-responses in individual glomeruli, and distributed odorant responses across a population of glomeruli. Comparisons between ArcLight and the protein calcium sensors GCaMP3 and GCaMP6f revealed that ArcLight had faster temporal kinetics that more clearly distinguished activity elicited by individual odorant inspirations. In contrast, the signals from both GCaMPs were a saturating integral of activity that returned relatively slowly to the baseline. ArcLight enables optical electrophysiology of mammalian neuronal population activity in vivo.
Highlights
Traditional optical imaging techniques using intrinsic signals[1,2] or organic dyes for measuring voltage[3] and calcium[4,5], are limited in their ability to distinguish the cell types contributing to the signal, except in special cases[6,7]
We tested whether ArcLight can be used as an in vivo reporter of the glomerular output via mitral/tufted cells, and compared it to the calcium sensors GCaMP3 and GCaMP6f
We report the in vivo response of the genetically encoded fluorescent protein (FP) voltage sensor, ArcLight[8], in the mammalian brain
Summary
Traditional optical imaging techniques using intrinsic signals[1,2] or organic dyes for measuring voltage[3] and calcium[4,5], are limited in their ability to distinguish the cell types contributing to the signal, except in special cases[6,7]. ArcLight is a protein voltage sensor that can detect single action potentials in cultured mammalian neurons[8], and in vivo in Caenorhabditis elegans[9] and Drosophila[10]. These results make ArcLight a strong candidate for in vivo functional imaging in mammalian preparations. Protein voltage sensors[11] resulted in poor expression in mammalian cells[12], and other sensors that worked well in mammalian cells in vitro[13,14] suffered from poor in vivo performance[15,16,17]
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