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      Using Head-Mounted Ethanol Sensors to Monitor Olfactory Information and Determine Behavioral Changes Associated with Ethanol-Plume Contact during Mouse Odor-Guided Navigation

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          Abstract

          Olfaction guides navigation and decision-making in organisms from multiple animal phyla. Understanding how animals use olfactory cues to guide navigation is a complicated problem for two main reasons. First, the sensory cues used to guide animals to the source of an odor consist of volatile molecules, which form plumes. These plumes are governed by turbulent air currents, resulting in an intermittent and spatiotemporally varying olfactory signal. A second problem is that the technologies for chemical quantification are cumbersome and cannot be used to detect what the freely moving animal senses in real time. Understanding how the olfactory system guides this behavior requires knowing the sensory cues and the accompanying brain signals during navigation. Here, we present a method for real-time monitoring of olfactory information using low-cost, lightweight sensors that robustly detect common solvent molecules, like alcohols, and can be easily mounted on the heads of freely behaving mice engaged in odor-guided navigation. To establish the accuracy and temporal response properties of these sensors we compared their responses with those of a photoionization detector (PID) to precisely controlled ethanol stimuli. Ethanol-sensor recordings, deconvolved using a difference-of-exponentials kernel, showed robust correlations with the PID signal at behaviorally relevant time, frequency, and spatial scales. Additionally, calcium imaging of odor responses from the olfactory bulbs (OBs) of awake, head-fixed mice showed strong correlations with ethanol plume contacts detected by these sensors. Finally, freely behaving mice engaged in odor-guided navigation showed robust behavioral changes such as speed reduction that corresponded to ethanol plume contacts.

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          Metal Oxide Gas Sensors: Sensitivity and Influencing Factors

          Conductometric semiconducting metal oxide gas sensors have been widely used and investigated in the detection of gases. Investigations have indicated that the gas sensing process is strongly related to surface reactions, so one of the important parameters of gas sensors, the sensitivity of the metal oxide based materials, will change with the factors influencing the surface reactions, such as chemical components, surface-modification and microstructures of sensing layers, temperature and humidity. In this brief review, attention will be focused on changes of sensitivity of conductometric semiconducting metal oxide gas sensors due to the five factors mentioned above.
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            Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data.

            We present a modular approach for analyzing calcium imaging recordings of large neuronal ensembles. Our goal is to simultaneously identify the locations of the neurons, demix spatially overlapping components, and denoise and deconvolve the spiking activity from the slow dynamics of the calcium indicator. Our approach relies on a constrained nonnegative matrix factorization that expresses the spatiotemporal fluorescence activity as the product of a spatial matrix that encodes the spatial footprint of each neuron in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time. This framework is combined with a novel constrained deconvolution approach that extracts estimates of neural activity from fluorescence traces, to create a spatiotemporal processing algorithm that requires minimal parameter tuning. We demonstrate the general applicability of our method by applying it to in vitro and in vivo multi-neuronal imaging data, whole-brain light-sheet imaging data, and dendritic imaging data.
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              Thy1-GCaMP6 Transgenic Mice for Neuronal Population Imaging In Vivo

              Genetically-encoded calcium indicators (GECIs) facilitate imaging activity of genetically defined neuronal populations in vivo. The high intracellular GECI concentrations required for in vivo imaging are usually achieved by viral gene transfer using adeno-associated viruses. Transgenic expression of GECIs promises important advantages, including homogeneous, repeatable, and stable expression without the need for invasive virus injections. Here we present the generation and characterization of transgenic mice expressing the GECIs GCaMP6s or GCaMP6f under the Thy1 promoter. We quantified GCaMP6 expression across brain regions and neurons and compared to other transgenic mice and AAV-mediated expression. We tested three mouse lines for imaging in the visual cortex in vivo and compared their performance to mice injected with AAV expressing GCaMP6. Furthermore, we show that GCaMP6 Thy1 transgenic mice are useful for long-term, high-sensitivity imaging in behaving mice.
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                Author and article information

                Journal
                eNeuro
                eNeuro
                eneuro
                eneuro
                eNeuro
                eNeuro
                Society for Neuroscience
                2373-2822
                8 January 2021
                15 January 2021
                Jan-Feb 2021
                : 8
                : 1
                : ENEURO.0285-20.2020
                Affiliations
                [1 ]Graduate Program in Neuroscience, University of Washington , Seattle, Washington 98195
                [2 ]Department of Psychology, University of Washington , Seattle, Washington 98195
                [3 ]Departments of Biology and Otolaryngology, University of Washington , Seattle, Washington 98195
                [4 ]University of Washington Institute for Neuroengineering , Seattle, Washington 98195
                Author notes

                The authors declare no competing financial interests.

                Author contributions: M.F.T., S.M.L., D.J.P., and D.H.G. designed research; M.F.T., S.M.L., A.L., and S.M. performed research; M.F.T., S.M.L., J.T.M., D.J.P., and D.H.G. analyzed data; M.F.T., J.T.M., D.J.P., and D.H.G. wrote the paper.

                This work was supported by the National Institutes of Health Grant R21DC018649, the University of Washington Innovation Award, and a FACE Foundation Thomas Jefferson Award (D.H.G.). M.F.T. was supported by The University of Washington Institute for Neuroengineering/Washington Research Foundation Innovation Graduate Fellowship and Auditory Neuroscience Training Grant T32DC005361.

                Correspondence should be addressed to David H. Gire at dhgire@ 123456uw.edu .
                Author information
                https://orcid.org/0000-0001-6962-1452
                https://orcid.org/0000-0002-3142-9614
                https://orcid.org/0000-0003-4119-4270
                Article
                eN-MNT-0285-20
                10.1523/ENEURO.0285-20.2020
                7877453
                33419862
                b101028d-5991-4d61-8633-7c5626f881aa
                Copyright © 2021 Tariq et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 29 June 2020
                : 14 December 2020
                : 17 December 2020
                Page count
                Figures: 8, Tables: 0, Equations: 9, References: 28, Pages: 12, Words: 00
                Funding
                Funded by: http://doi.org/10.13039/100000055HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)
                Award ID: R21DC018649
                Award ID: T32DC005361
                Funded by: University of Washington Innovation Award
                Funded by: FACE Foundation Thomas Jefferson Award
                Funded by: UWIN/WRF Innovation Graduate Fellowship
                Categories
                7
                Research Article: Methods/New Tools
                Novel Tools and Methods
                Custom metadata
                January/February 2021

                behavior,foraging,navigation,olfaction,sensory
                behavior, foraging, navigation, olfaction, sensory

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