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      Trigeminal Contributions to the Dorsal Cochlear Nucleus in Mouse

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          Abstract

          The dorsal cochlear nucleus (DCN) is the first site of multisensory integration in the auditory pathway of mammals. The DCN circuit integrates non-auditory information, such as head and ear position, with auditory signals, and this convergence may contribute to the ability to localize sound sources or to suppress perceptions of self-generated sounds. Several extrinsic sources of these non-auditory signals have been described in various species, and among these are first- and second-order trigeminal axonal projections. Trigeminal sensory signals from the face and ears could provide the non-auditory information that the DCN requires for its role in sound source localization and cancelation of self-generated sounds, for example, head and ear position or mouth movements that could predict the production of chewing or licking sounds. There is evidence for these axonal projections in guinea pigs and rats, although the size of the pathway is smaller than might be expected for a function essential for a prey animals’ survival. However, evidence for these projections in mice, an increasingly important species in auditory neuroscience, is lacking, raising questions about the universality of such proposed functions. We therefore investigated the presence of trigeminal projections to the DCN in mice, using viral and transgenic approaches. We found that the spinal trigeminal nucleus indeed projects to DCN, targeting granule cells and unipolar brush cells. However, direct axonal projections from the trigeminal ganglion itself were undetectable. Thus, secondary brainstem sources carry non-auditory signals to the DCN in mice that could provide a processed trigeminal signal to the DCN, but primary trigeminal afferents are not integrated directly by DCN.

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          Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy.

          Lateral resolution that exceeds the classical diffraction limit by a factor of two is achieved by using spatially structured illumination in a wide-field fluorescence microscope. The sample is illuminated with a series of excitation light patterns, which cause normally inaccessible high-resolution information to be encoded into the observed image. The recorded images are linearly processed to extract the new information and produce a reconstruction with twice the normal resolution. Unlike confocal microscopy, the resolution improvement is achieved with no need to discard any of the emission light. The method produces images of strikingly increased clarity compared to both conventional and confocal microscopes.
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            Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems

            Adeno-associated viruses (AAVs) are commonly used for in vivo gene transfer. Nevertheless, AAVs that provide efficient transduction across specific organs or cell populations are needed. Here, we describe AAV-PHP.eB and AAV-PHP.S, capsids that efficiently transduce the central and peripheral nervous systems, respectively. In the adult mouse, intravenous administration of 1×1011 vector genomes (vg) of AAV-PHP.eB transduced 69% of cortical and 55% of striatal neurons, while 1×1012 vg AAV-PHP.S transduced 82% of dorsal root ganglion neurons, as well as cardiac and enteric neurons. The efficiency of these vectors facilitates robust co-transduction and stochastic, multicolor labeling for individual cell morphology studies. To support such efforts, we provide methods for labeling a tunable fraction of cells without compromising color diversity. Furthermore, when used with cell type-specific promoters, these AAVs provide targeted gene expression across the nervous system and enable efficient and versatile gene manipulation throughout the nervous system of transgenic and non-transgenic animals.
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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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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                28 July 2021
                2021
                : 15
                : 715954
                Affiliations
                Vollum Institute and Oregon Hearing Research Center, Oregon Health & Science University , Portland, OR, United States
                Author notes

                Edited by: David Pérez-González, University of Salamanca, Spain

                Reviewed by: Jeffrey Garrett Mellott, Northeast Ohio Medical University, United States; Huizhong Whit Tao, University of Southern California, United States

                *Correspondence: Laurence O. Trussell, trussell@ 123456ohsu.edu

                Present address: Timothy S. Balmer, School of Life Sciences, Arizona State University, Tempe, AZ, United States

                This article was submitted to Auditory Cognitive Neuroscience, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2021.715954
                8357187
                34393720
                69532f48-7774-4248-ae9c-4d50bb6eb244
                Copyright © 2021 Balmer and Trussell.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 May 2021
                : 07 July 2021
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 24, Pages: 8, Words: 0
                Funding
                Funded by: National Institute on Deafness and Other Communication Disorders 10.13039/100000055
                Funded by: National Institute on Deafness and Other Communication Disorders 10.13039/100000055
                Categories
                Neuroscience
                Original Research

                Neurosciences
                dorsal cochlear nucleus,trigeminal,granule cell,mouse,auditory
                Neurosciences
                dorsal cochlear nucleus, trigeminal, granule cell, mouse, auditory

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