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      Neuronal pattern separation in the olfactory bulb improves odor discrimination learning

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          Abstract

          Neuronal pattern separation is thought to enable the brain to disambiguate sensory stimuli with overlapping features thereby extracting valuable information. In the olfactory system, it remains unknown whether pattern separation acts as a driving force for sensory discrimination and the learning thereof. Here we show that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) are dynamically reformatted in the network at the timescale of a single breath, giving rise to separated patterns of activity in ensemble of output neurons (mitral/tufted cells; M/T). Strikingly, the extent of pattern separation in M/T assemblies predicts behavioral discrimination performance during the learning phase. Furthermore, exciting or inhibiting GABAergic OB interneurons, using optogenetics or pharmacogenetics, altered pattern separation and thereby odor discrimination learning in a bidirectional way. In conclusion, we propose that the OB network can act as a pattern separator facilitating olfactory stimuli distinction, a process that is sculpted by synaptic inhibition.

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          Most cited references44

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          Pattern separation in the dentate gyrus and CA3 of the hippocampus.

          Theoretical models have long pointed to the dentate gyrus as a possible source of neuronal pattern separation. In agreement with predictions from these models, we show that minimal changes in the shape of the environment in which rats are exploring can substantially alter correlated activity patterns among place-modulated granule cells in the dentate gyrus. When the environments are made more different, new cell populations are recruited in CA3 but not in the dentate gyrus. These results imply a dual mechanism for pattern separation in which signals from the entorhinal cortex can be decorrelated both by changes in coincidence patterns in the dentate gyrus and by recruitment of nonoverlapping cell assemblies in CA3.
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            Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion.

            Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks after functional integration into the neuronal network, distinguishing them from less active, older adult-born GCs and the major population of dentate GCs generated developmentally. To ascertain whether young and old GCs perform distinct memory functions, we created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts, which was reduced following ablation of young GCs. Furthermore, these mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation requires adult-born young GCs but not old GCs, and older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network.

              Forming distinct representations of multiple contexts, places, and episodes is a crucial function of the hippocampus. The dentate gyrus subregion has been suggested to fulfill this role. We have tested this hypothesis by generating and analyzing a mouse strain that lacks the gene encoding the essential subunit of the N-methyl-d-aspartate (NMDA) receptor NR1, specifically in dentate gyrus granule cells. The mutant mice performed normally in contextual fear conditioning, but were impaired in the ability to distinguish two similar contexts. A significant reduction in the context-specific modulation of firing rate was observed in the CA3 pyramidal cells when the mutant mice were transferred from one context to another. These results provide evidence that NMDA receptors in the granule cells of the dentate gyrus play a crucial role in the process of pattern separation.
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                Author and article information

                Journal
                9809671
                21092
                Nat Neurosci
                Nat. Neurosci.
                Nature neuroscience
                1097-6256
                1546-1726
                3 August 2015
                24 August 2015
                October 2015
                26 April 2016
                : 18
                : 10
                : 1474-1482
                Affiliations
                [1 ]Department of Basic Neurosciences, School of Medicine, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland
                [2 ]Geneva Neuroscience Center, University of Geneva, Switzerland
                [3 ]Department of Genetics and Evolution, University of Geneva, 1211 Geneva, Switzerland
                [4 ]Firmenich SA, Corporate R&D Division / Analytical Innovation, route des Jeunes 1, CH-1211 Geneva 8, Switzerland
                Author notes
                Correspondence should be addressed to A.C. ( alan.carleton@ 123456unige.ch ) or I.R. ( ivan.rodriguez@ 123456unige.ch )

                AUTHOR CONTRIBUTIONS

                O.G., N.A., S.L., I.R. and A.C. carried out the study conceptualization and experimental design. O.G. acquired and analyzed electrophysiological data. S.L. acquired and analyzed imaging data. N.A. performed and analyzed behavioral experiments. O.G. and N.A. performed virus injection, window implantation, opto/pharmacogenetics and related behavior, immunohistochemistry, confocal imaging and quantification. N.A. and F.B. acquired and analyzed GC-FID data. O.G. and A.C. wrote the manuscript with comments from N.A., S.L., F.B. and I.R.

                Article
                EMS64374
                10.1038/nn.4089
                4845880
                26301325
                62003b99-d114-48a3-a963-584af43d9971

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                Neurosciences
                population coding,in-vivo extracellular recording,head-restrained behavior,optogenetics,odorant mixture

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