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      Sensory overamplification in layer 5 auditory corticofugal projection neurons following cochlear nerve synaptic damage

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          Abstract

          Layer 5 (L5) cortical projection neurons innervate far-ranging brain areas to coordinate integrative sensory processing and adaptive behaviors. Here, we characterize a plasticity in L5 auditory cortex (ACtx) neurons that innervate the inferior colliculus (IC), thalamus, lateral amygdala and striatum. We track daily changes in sound processing using chronic widefield calcium imaging of L5 axon terminals on the dorsal cap of the IC in awake, adult mice. Sound level growth functions at the level of the auditory nerve and corticocollicular axon terminals are both strongly depressed hours after noise-induced damage of cochlear afferent synapses. Corticocollicular response gain rebounded above baseline levels by the following day and remained elevated for several weeks despite a persistent reduction in auditory nerve input. Sustained potentiation of excitatory ACtx projection neurons that innervate multiple limbic and subcortical auditory centers may underlie hyperexcitability and aberrant functional coupling of distributed brain networks in tinnitus and hyperacusis.

          Abstract

          Deep layer auditory cortex neurons project to a number of limbic and subcortical auditory structures. Here, the authors show how these corticofugal projections adjust response gain following noise-induced cochlear damage.

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          Most cited references63

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          The neocortical circuit: themes and variations.

          Similarities in neocortical circuit organization across areas and species suggest a common strategy to process diverse types of information, including sensation from diverse modalities, motor control and higher cognitive processes. Cortical neurons belong to a small number of main classes. The properties of these classes, including their local and long-range connectivity, developmental history, gene expression, intrinsic physiology and in vivo activity patterns, are remarkably similar across areas. Each class contains subclasses; for a rapidly growing number of these, conserved patterns of input and output connections are also becoming evident. The ensemble of circuit connections constitutes a basic circuit pattern that appears to be repeated across neocortical areas, with area- and species-specific modifications. Such 'serially homologous' organization may adapt individual neocortical regions to the type of information each must process.
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            AAV-Mediated Anterograde Transsynaptic Tagging: Mapping Corticocollicular Input-Defined Neural Pathways for Defense Behaviors.

            To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we discovered that adeno-associated viruses (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drives Cre-dependent transgene expression in selected postsynaptic neuronal targets, thus allowing axonal tracing and functional manipulations of the latter input-defined neuronal population. Its application in superior colliculus (SC) reveals that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drive flight and freezing, two different types of defense behavior, respectively. Together with an intersectional approach, AAV-mediated anterograde transsynaptic tagging can categorize neurons by their inputs and molecular identity, and allow forward screening of distinct functional neural pathways embedded in complex brain circuits.
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              Cortical connectivity and sensory coding.

              The sensory cortex contains a wide array of neuronal types, which are connected together into complex but partially stereotyped circuits. Sensory stimuli trigger cascades of electrical activity through these circuits, causing specific features of sensory scenes to be encoded in the firing patterns of cortical populations. Recent research is beginning to reveal how the connectivity of individual neurons relates to the sensory features they encode, how differences in the connectivity patterns of different cortical cell classes enable them to encode information using different strategies, and how feedback connections from higher-order cortex allow sensory information to be integrated with behavioural context.
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                Author and article information

                Contributors
                masokan@g.harvard.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                25 June 2018
                25 June 2018
                2018
                : 9
                : 2468
                Affiliations
                [1 ]ISNI 0000 0000 8800 3003, GRID grid.39479.30, Eaton-Peabody Laboratories, , Massachusetts Eye and Ear Infirmary, ; Boston, MA 02114 USA
                [2 ]ISNI 000000041936754X, GRID grid.38142.3c, Division of Medical Sciences, , Harvard University, ; Boston, MA 02114 USA
                [3 ]ISNI 000000041936754X, GRID grid.38142.3c, Department of Otolaryngology, , Harvard Medical School, ; Boston, MA 02114 USA
                Article
                4852
                10.1038/s41467-018-04852-y
                6018400
                29317637
                6c7f1c21-0de7-4c8b-b09b-3801d9f0ccf5
                © 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
                : 6 July 2017
                : 24 May 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000055, U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD);
                Award ID: DC009836
                Award Recipient :
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                © The Author(s) 2018

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