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      Sparsened neuronal activity in an optogenetically activated olfactory glomerulus

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          Abstract

          Glomeruli are the functional units of olfactory information processing but little remains known about their individual unit function. This is due to their widespread activation by odor stimuli. We expressed channelrhodopsin-2 in a single olfactory sensory neuron type, and used laser stimulation and simultaneous in vivo calcium imaging to study the responses of a single glomerulus to optogenetic stimulation. Calcium signals in the neuropil of this glomerulus were representative of the sensory input and nearly identical if evoked by intensity-matched odor and laser stimuli. However, significantly fewer glomerular layer interneurons and olfactory bulb output neurons (mitral cells) responded to optogenetic versus odor stimuli, resulting in a small and spatially compact optogenetic glomerular unit response. Temporal features of laser stimuli were represented with high fidelity in the neuropil of the glomerulus and the mitral cells, but not in interneurons. Increases in laser stimulus intensity were encoded by larger signal amplitudes in all compartments of the glomerulus, and by the recruitment of additional interneurons and mitral cells. No spatial expansion of the glomerular unit response was observed in response to stronger input stimuli. Our data are among the first descriptions of input-output transformations in a selectively activated olfactory glomerulus.

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          Most cited references37

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          Odor coding by a Mammalian receptor repertoire.

          Deciphering olfactory encoding requires a thorough description of the ligands that activate each odorant receptor (OR). In mammalian systems, however, ligands are known for fewer than 50 of more than 1400 human and mouse ORs, greatly limiting our understanding of olfactory coding. We performed high-throughput screening of 93 odorants against 464 ORs expressed in heterologous cells and identified agonists for 52 mouse and 10 human ORs. We used the resulting interaction profiles to develop a predictive model relating physicochemical odorant properties, OR sequences, and their interactions. Our results provide a basis for translating odorants into receptor neuron responses and for unraveling mammalian odor coding.
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            Representation of odorants by receptor neuron input to the mouse olfactory bulb.

            To visualize odorant representations by receptor neuron input to the mouse olfactory bulb, we loaded receptor neurons with calcium-sensitive dye and imaged odorant-evoked responses from their axon terminals. Fluorescence increases reflected activation of receptor neuron populations converging onto individual glomeruli. We report several findings. First, five glomeruli were identifiable across animals based on their location and odorant responsiveness; all five showed complex response specificities. Second, maps of input were chemotopically organized at near-threshold concentrations but, at moderate concentrations, involved many widely distributed glomeruli. Third, the dynamic range of input to a glomerulus was greater than that reported for individual receptor neurons. Finally, odorant activation slopes could differ across glomeruli, and for different odorants activating the same glomerulus. These results imply a high degree of complexity in odorant representations at the level of olfactory bulb input.
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              Optical imaging of odorant representations in the mammalian olfactory bulb.

              We adapted the technique of intrinsic signal imaging to visualize how odorant concentration and structure are represented spatially in the rat olfactory bulb. Most odorants activated one or more glomeruli in the imaged region of the bulb; these optically imaged responses reflected the excitation of underlying neurons. Odorant-evoked patterns were similar across animals and symmetrical in the two bulbs of the same animal. The variable sensitivity of individual glomeruli produced distinct maps for different odorant concentrations. Using a series of homologous aldehydes, we found that glomeruli were tuned to detect particular molecular features and that maps of similar molecules were highly correlated. These characteristics suggest that odorants and their concentrations can be encoded by distinct spatial patterns of glomerular activation.
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                Author and article information

                Contributors
                obraubach@icloud.com
                lawrence.b.cohen@hotmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                8 October 2018
                8 October 2018
                2018
                : 8
                : 14955
                Affiliations
                [1 ]ISNI 0000000121053345, GRID grid.35541.36, Center for Functional Connectomics, , Brain Science Institute, Korea Institute of Science and Technology (KIST), ; Seoul, 136-791 Korea
                [2 ]ISNI 0000000419368710, GRID grid.47100.32, Department of Cellular and Molecular Physiology, , Yale University School of Medicine, ; New Haven, CT 06510 USA
                [3 ]ISNI 000000012169920X, GRID grid.144532.5, NeuroImaging Cluster, , Marine Biological Laboratory, ; Woods Hole, MA 02543 USA
                [4 ]Department of Neurosurgery, Cedars Sinai Medical Institute, Los Angeles, CA 90048 USA
                [5 ]ISNI 0000 0001 2299 3507, GRID grid.16753.36, Department of Neurobiology, , Northwestern University, ; Evanston, IL 60208 USA
                [6 ]ISNI 0000 0001 2167 1581, GRID grid.413575.1, Visiting Scientist Program, , HHMI Janelia Farm Research Campus, ; Ashburn, VA 20147 USA
                Author information
                http://orcid.org/0000-0003-2038-7954
                http://orcid.org/0000-0002-6574-8154
                Article
                33021
                10.1038/s41598-018-33021-w
                6175855
                30297851
                7e353cbe-27ac-4fb9-b69b-8f498c487a75
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 May 2018
                : 7 September 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003725, National Research Foundation of Korea (NRF);
                Award ID: WCI 2009-003
                Award ID: WCI 2009-003
                Award Recipient :
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