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Loss of oligodendrocyte ErbB receptor signaling leads to hypomyelination, reduced density of parvalbumin-expressing interneurons, and inhibitory function in the auditory cortex

dc.contributor.authorBorges, Beatriz C.
dc.contributor.authorMeng, Xiangying
dc.contributor.authorLong, Patrick
dc.contributor.authorKanold, Patrick O.
dc.contributor.authorCorfas, Gabriel
dc.date.accessioned2023-01-11T16:28:28Z
dc.date.available2024-03-11 11:28:23en
dc.date.available2023-01-11T16:28:28Z
dc.date.issued2023-02
dc.identifier.citationBorges, Beatriz C.; Meng, Xiangying; Long, Patrick; Kanold, Patrick O.; Corfas, Gabriel (2023). "Loss of oligodendrocyte ErbB receptor signaling leads to hypomyelination, reduced density of parvalbumin-expressing interneurons, and inhibitory function in the auditory cortex." Glia 71(2): 187-204.
dc.identifier.issn0894-1491
dc.identifier.issn1098-1136
dc.identifier.urihttps://hdl.handle.net/2027.42/175535
dc.description.abstractFor a long time, myelin was thought to be restricted to excitatory neurons, and studies on dysmyelination focused primarily on excitatory cells. Recent evidence showed that axons of inhibitory neurons in the neocortex are also myelinated, but the role of myelin on inhibitory circuits remains unknown. Here we studied the impact of mild hypomyelination on both excitatory and inhibitory connectivity in the primary auditory cortex (A1) with well-characterized mouse models of hypomyelination due to loss of oligodendrocyte ErbB receptor signaling. Using laser-scanning photostimulation, we found that mice with mild hypomyelination have reduced functional inhibitory connections to A1 L2/3 neurons without changes in excitatory connections, resulting in altered excitatory/inhibitory balance. These effects are not associated with altered expression of GABAergic and glutamatergic synaptic components, but with reduced density of parvalbumin-positive (PV+) neurons, axons, and synaptic terminals, which reflect reduced PV expression by interneurons rather than PV+ neuronal loss. While immunostaining shows that hypomyelination occurs in both PV+ and PV− axons, there is a strong correlation between MBP and PV expression, suggesting that myelination influences PV expression. Together, the results indicate that mild hypomyelination impacts A1 neuronal networks, reducing inhibitory activity, and shifting networks towards excitation.Main PointLoss of oligodendrocyte ErbB receptor signaling leads to A1 hypomyelination, reduced PV expression and density of PV+ neurons and synapses, hypoconnectivity of inhibitory circuits and shift of the E/I balance towards excitation.
dc.publisherJohn Wiley & Sons, Inc.
dc.subject.otherauditory cortex
dc.subject.othercircuit
dc.subject.otherE/I balance
dc.subject.otherinhibition
dc.subject.othermyelin basic protein
dc.subject.otheroligodendrocytes
dc.titleLoss of oligodendrocyte ErbB receptor signaling leads to hypomyelination, reduced density of parvalbumin-expressing interneurons, and inhibitory function in the auditory cortex
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biology
dc.subject.hlbsecondlevelNeurosciences
dc.subject.hlbsecondlevelPublic Health
dc.subject.hlbtoplevelHealth Sciences
dc.subject.hlbtoplevelScience
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175535/1/glia24266_am.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175535/2/glia24266.pdf
dc.identifier.doi10.1002/glia.24266
dc.identifier.sourceGlia
dc.identifier.citedreferenceRio, C., Rieff, H. I., Qi, P., Khurana, T. S., & Corfas, G. ( 1997 ). Neuregulin and erbB receptors play a critical role in neuronal migration. Neuron, 19 ( 1 ), 39 – 50. https://doi.org/10.1016/s0896-6273(00)80346-3
dc.identifier.citedreferenceMeng, X., Solarana, K., Bowen, Z., Liu, J., Nagode, D. A., Sheikh, A., & Kanold, P. O. ( 2020 ). Transient subgranular hyperconnectivity to L2/3 and enhanced pairwise correlations during the critical period in the mouse auditory cortex. Cerebral Cortex, 30 ( 3 ), 1914 – 1930. https://doi.org/10.1093/cercor/bhz213
dc.identifier.citedreferenceMeng, X., Winkowski, D. E., Kao, J. P. Y., & Kanold, P. O. ( 2017 ). Sublaminar subdivision of mouse auditory cortex layer 2/3 based on functional translaminar connections. The Journal of Neuroscience, 37 ( 42 ), 10200 – 10214. https://doi.org/10.1523/JNEUROSCI.1361-17.2017
dc.identifier.citedreferenceMeuth, S. G., Bittner, S., Ulzheimer, J. C., Kleinschnitz, C., Kieseier, B. C., & Wiendl, H. ( 2010 ). Therapeutic approaches to multiple sclerosis: An update on failed, interrupted, or inconclusive trials of neuroprotective and alternative treatment strategies. BioDrugs, 24 ( 5 ), 317 – 330. https://doi.org/10.2165/11537190-000000000-00000
dc.identifier.citedreferenceMicheva, K. D., Wolman, D., Mensh, B. D., Pax, E., Buchanan, J., Smith, S. J., & Bock, D. D. ( 2016 ). A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons. eLife, 5, 1 – 29. https://doi.org/10.7554/eLife.15784
dc.identifier.citedreferenceMonje, M. ( 2018 ). Myelin plasticity and nervous system function. Annual Review of Neuroscience, 41, 61 – 76. https://doi.org/10.1146/annurev-neuro-080317-061853
dc.identifier.citedreferenceMuralidharan, S., Dirda, N. D., Katz, E. J., Tang, C. M., Bandyopadhyay, S., Kanold, P. O., & Kao, J. P. ( 2016 ). NCM, a photolabile group for preparation of caged molecules: Synthesis and biological application. PLoS One, 11 ( 10 ), e0163937. https://doi.org/10.1371/journal.pone.0163937
dc.identifier.citedreferenceNarayanan, V., Cerina, M., Gobel, K., Meuth, P., Herrmann, A. M., Fernandez-Orth, J., & Pape, H. C. ( 2018 ). Impairment of frequency-specific responses associated with altered electrical activity patterns in auditory thalamus following focal and general demyelination. Experimental Neurology, 309, 54 – 66. https://doi.org/10.1016/j.expneurol.2018.07.010
dc.identifier.citedreferencePeters, A., & Proskauer, C. C. ( 1980 ). Synaptic relationships between a multipolar stellate cell and a pyramidal neuron in the rat visual cortex. A combined Golgi-electron microscope study. Journal of Neurocytology, 9 ( 2 ), 163 – 183. https://doi.org/10.1007/BF01205156
dc.identifier.citedreferencePrevot, V., Rio, C., Cho, G. J., Lomniczi, A., Heger, S., Neville, C. M., & Corfas, G. ( 2003 ). Normal female sexual development requires neuregulin-erbB receptor signaling in hypothalamic astrocytes. The Journal of Neuroscience, 23 ( 1 ), 230 – 239.
dc.identifier.citedreferenceQu, S., Rinehart, C., Wu, H. H., Wang, S. E., Carter, B., Xin, H., & Arteaga, C. L. ( 2006 ). Gene targeting of ErbB3 using a Cre-mediated unidirectional DNA inversion strategy. Genesis, 44 ( 10 ), 477 – 486. https://doi.org/10.1002/dvg.20243
dc.identifier.citedreferenceQue, L., Lukacsovich, D., Luo, W., & Foldy, C. ( 2021 ). Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus. Nature Communications, 12 ( 1 ), 108. https://doi.org/10.1038/s41467-020-20328-4
dc.identifier.citedreferenceRinholm, J. E., Hamilton, N. B., Kessaris, N., Richardson, W. D., Bergersen, L. H., & Attwell, D. ( 2011 ). Regulation of oligodendrocyte development and myelination by glucose and lactate. The Journal of Neuroscience, 31 ( 2 ), 538 – 548. https://doi.org/10.1523/JNEUROSCI.3516-10.2011
dc.identifier.citedreferenceRotschafer, S. E. ( 2021 ). Auditory discrimination in autism spectrum disorder. Frontiers in Neuroscience, 15, 651209. https://doi.org/10.3389/fnins.2021.651209
dc.identifier.citedreferenceRoy, K., Murtie, J. C., El-Khodor, B. F., Edgar, N., Sardi, S. P., Hooks, B. M., & Corfas, G. ( 2007 ). Loss of erbB signaling in oligodendrocytes alters myelin and dopaminergic function, a potential mechanism for neuropsychiatric disorders. Proceedings of the National Academy of Sciences of the United States of America, 104 ( 19 ), 8131 – 8136. https://doi.org/10.1073/pnas.0702157104
dc.identifier.citedreferenceSommeijer, J. P., & Levelt, C. N. ( 2012 ). Synaptotagmin-2 is a reliable marker for parvalbumin positive inhibitory boutons in the mouse visual cortex. PLoS One, 7 ( 4 ), e35323. https://doi.org/10.1371/journal.pone.0035323
dc.identifier.citedreferenceSrinivasan, V., Udayakumar, N., & Anandan, K. ( 2020 ). Influence of primary auditory cortex in the characterization of autism Spectrum in young adults using brain connectivity parameters and deep belief networks: An fMRI study. Current Medical Imaging, 16 ( 9 ), 1059 – 1073. https://doi.org/10.2174/1573405615666191111142039
dc.identifier.citedreferenceStankovic, K. M., & Corfas, G. ( 2003 ). Real-time quantitative RT-PCR for low-abundance transcripts in the inner ear: Analysis of neurotrophic factor expression. Hearing Research, 185 ( 1–2 ), 97 – 108. https://doi.org/10.1016/s0378-5955(03)00298-3
dc.identifier.citedreferenceStedehouder, J., Brizee, D., Shpak, G., & Kushner, S. A. ( 2018 ). Activity-dependent myelination of parvalbumin interneurons mediated by axonal morphological plasticity. The Journal of Neuroscience, 38 ( 15 ), 3631 – 3642. https://doi.org/10.1523/JNEUROSCI.0074-18.2018
dc.identifier.citedreferenceStedehouder, J., Brizee, D., Slotman, J. A., Pascual-Garcia, M., Leyrer, M. L., Bouwen, B. L., & Kushner, S. A. ( 2019 ). Local axonal morphology guides the topography of interneuron myelination in mouse and human neocortex. eLife, 8, 1 – 28. https://doi.org/10.7554/eLife.48615
dc.identifier.citedreferenceStedehouder, J., Couey, J. J., Brizee, D., Hosseini, B., Slotman, J. A., Dirven, C. M. F., & Kushner, S. A. ( 2017 ). Fast-spiking parvalbumin interneurons are frequently myelinated in the cerebral cortex of mice and humans. Cerebral Cortex, 27 ( 10 ), 5001 – 5013. https://doi.org/10.1093/cercor/bhx203
dc.identifier.citedreferenceStedehouder, J., & Kushner, S. A. ( 2017 ). Myelination of parvalbumin interneurons: A parsimonious locus of pathophysiological convergence in schizophrenia. Molecular Psychiatry, 22 ( 1 ), 4 – 12. https://doi.org/10.1038/mp.2016.147
dc.identifier.citedreferenceSteinman, G., & Mankuta, D. ( 2019 ). Molecular biology of autism’s etiology - an alternative mechanism. Medical Hypotheses, 130, 109272. https://doi.org/10.1016/j.mehy.2019.109272
dc.identifier.citedreferenceSuter, B. A., O’Connor, T., Iyer, V., Petreanu, L. T., Hooks, B. M., Kiritani, T., Svoboda, K., & Shepherd, G. M. ( 2010 ). Ephus: multipurpose data acquisition software for neuroscience experiments. Frontiers in Neural Circuits, 4, 100. https://doi.org/10.3389/fncir.2010.00100
dc.identifier.citedreferenceTamas, G., Buhl, E. H., & Somogyi, P. ( 1997 ). Fast IPSPs elicited via multiple synaptic release sites by different types of GABAergic neurone in the cat visual cortex. The Journal of Physiology, 500 ( 3 ), 715 – 738. https://doi.org/10.1113/jphysiol.1997.sp022054
dc.identifier.citedreferenceUeno, H., Shoshi, C., Suemitsu, S., Usui, S., Sujiura, H., & Okamoto, M. ( 2013 ). Somatosensory and visual deprivation each decrease the density of parvalbumin neurons and their synapse terminals in the prefrontal cortex and hippocampus of mice. Acta Medica Okayama, 67 ( 3 ), 135 – 143. https://doi.org/10.18926/AMO/50406
dc.identifier.citedreferenceWang, X., Lu, T., Bendor, D., & Bartlett, E. ( 2008 ). Neural coding of temporal information in auditory thalamus and cortex. Neuroscience, 154 ( 1 ), 294 – 303. https://doi.org/10.1016/j.neuroscience.2008.03.065
dc.identifier.citedreferenceYang, S. M., Michel, K., Jokhi, V., Nedivi, E., & Arlotta, P. ( 2020 ). Neuron class-specific responses govern adaptive myelin remodeling in the neocortex. Science, 370 ( 6523 ), 1 – 10. https://doi.org/10.1126/science.abd2109
dc.identifier.citedreferenceYau, H. J., Wang, H. F., Lai, C., & Liu, F. C. ( 2003 ). Neural development of the neuregulin receptor ErbB4 in the cerebral cortex and the hippocampus: Preferential expression by interneurons tangentially migrating from the ganglionic eminences. Cerebral Cortex, 13 ( 3 ), 252 – 264. https://doi.org/10.1093/cercor/13.3.252
dc.identifier.citedreferenceBragina, L., Fattorini, G., Giovedi, S., Melone, M., Bosco, F., Benfenati, F., & Conti, F. ( 2011 ). Analysis of synaptotagmin, SV2, and Rab3 expression in cortical glutamatergic and GABAergic axon terminals. Frontiers in Cellular Neuroscience, 5, 32.
dc.identifier.citedreferenceCerina, M., Narayanan, V., Gobel, K., Bittner, S., Ruck, T., Meuth, P., & Meuth, S. G. ( 2017 ). The quality of cortical network function recovery depends on localization and degree of axonal demyelination. Brain, Behavior, and Immunity, 59, 103 – 117. https://doi.org/10.1016/j.bbi.2016.08.014
dc.identifier.citedreferenceChen, S., Velardez, M. O., Warot, X., Yu, Z. X., Miller, S. J., Cros, D., & Corfas, G. ( 2006 ). Neuregulin 1-erbB signaling is necessary for normal myelination and sensory function. The Journal of Neuroscience, 26 ( 12 ), 3079 – 3086. https://doi.org/10.1523/jneurosci.3785-05.2006
dc.identifier.citedreferenceBenamer, N., Vidal, M., Balia, M., & Angulo, M. C. ( 2020 ). Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits. Nature Communications, 11 ( 1 ), 5151. https://doi.org/10.1038/s41467-020-18984-7
dc.identifier.citedreferenceBendor, D. ( 2015 ). The role of inhibition in a computational model of an auditory cortical neuron during the encoding of temporal information. PLoS Computational Biology, 11 ( 4 ), e1004197. https://doi.org/10.1371/journal.pcbi.1004197
dc.identifier.citedreferenceDehorter, N., Ciceri, G., Bartolini, G., Lim, L., del Pino, I., & Marin, O. ( 2015 ). Tuning of fast-spiking interneuron properties by an activity-dependent transcriptional switch. Science, 349 ( 6253 ), 1216 – 1220. https://doi.org/10.1126/science.aab3415
dc.identifier.citedreferenceDoerflinger, N. H., Macklin, W. B., & Popko, B. ( 2003 ). Inducible site-specific recombination in myelinating cells. Genesis, 35 ( 1 ), 63 – 72. https://doi.org/10.1002/gene.10154
dc.identifier.citedreferenceDrake, C. T., Mulligan, K. A., Wimpey, T. L., Hendrickson, A., & Chavkin, C. ( 1991 ). Characterization of Vicia villosa agglutinin-labeled GABAergic interneurons in the hippocampal formation and in acutely dissociated hippocampus. Brain Research, 554 ( 1–2 ), 176 – 185. https://doi.org/10.1016/0006-8993(91)90186-y
dc.identifier.citedreferenceDu, F., & Ongur, D. ( 2013 ). Probing myelin and axon abnormalities separately in psychiatric disorders using MRI techniques. Frontiers in Integrative Neuroscience, 7, 24.
dc.identifier.citedreferenceFavuzzi, E., Marques-Smith, A., Deogracias, R., Winterflood, C. M., Sanchez-Aguilera, A., Mantoan, L., & Rico, B. ( 2017 ). Activity-dependent gating of parvalbumin interneuron function by the perineuronal net protein brevican. Neuron, 95 ( 3 ), 639 – 655, e610. https://doi.org/10.1016/j.neuron.2017.06.028
dc.identifier.citedreferenceFilice, F., Vorckel, K. J., Sungur, A. O., Wohr, M., & Schwaller, B. ( 2016 ). Reduction in parvalbumin expression not loss of the parvalbumin-expressing GABA interneuron subpopulation in genetic parvalbumin and shank mouse models of autism. Molecular Brain, 9, 10. https://doi.org/10.1186/s13041-016-0192-8
dc.identifier.citedreferenceFoster, A. Y., Bujalka, H., & Emery, B. ( 2019 ). Axoglial interactions in myelin plasticity: Evaluating the relationship between neuronal activity and oligodendrocyte dynamics. Glia, 67 ( 11 ), 2038 – 2049. https://doi.org/10.1002/glia.23629
dc.identifier.citedreferenceGerecke, K. M., Wyss, J. M., Karavanova, I., Buonanno, A., & Carroll, S. L. ( 2001 ). ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system. The Journal of Comparative Neurology, 433 ( 1 ), 86 – 100. https://doi.org/10.1002/cne.1127
dc.identifier.citedreferenceGhaffarian, N., Mesgari, M., Cerina, M., Gobel, K., Budde, T., Speckmann, E. J., & Gorji, A. ( 2016 ). Thalamocortical-auditory network alterations following cuprizone-induced demyelination. Journal of Neuroinflammation, 13 ( 1 ), 160. https://doi.org/10.1186/s12974-016-0629-0
dc.identifier.citedreferenceGibson, E. M., Geraghty, A. C., & Monje, M. ( 2018 ). Bad wrap: Myelin and myelin plasticity in health and disease. Developmental Neurobiology, 78 ( 2 ), 123 – 135. https://doi.org/10.1002/dneu.22541
dc.identifier.citedreferenceGibson, E. M., Purger, D., Mount, C. W., Goldstein, A. K., Lin, G. L., Wood, L. S., & Monje, M. ( 2014 ). Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science, 344 ( 6183 ), 1252304. https://doi.org/10.1126/science.1252304
dc.identifier.citedreferenceGraciarena, M., Seiffe, A., Nait-Oumesmar, B., & Depino, A. M. ( 2018 ). Hypomyelination and oligodendroglial alterations in a mouse model of autism spectrum disorder. Frontiers in Cellular Neuroscience, 12, 517. https://doi.org/10.3389/fncel.2018.00517
dc.identifier.citedreferenceHu, H., Gan, J., & Jonas, P. ( 2014 ). Interneurons. Fast-spiking, parvalbumin(+) GABAergic interneurons: From cellular design to microcircuit function. Science, 345 ( 6196 ), 1255263. https://doi.org/10.1126/science.1255263
dc.identifier.citedreferenceJones, M. K., Kraus, N., Bonacina, S., Nicol, T., Otto-Meyer, S., & Roberts, M. Y. ( 2020 ). Auditory processing differences in toddlers with autism spectrum disorder. Journal of Speech, Language, and Hearing Research, 63 ( 5 ), 1608 – 1617. https://doi.org/10.1044/2020_JSLHR-19-00061
dc.identifier.citedreferenceLagler, M., Ozdemir, A. T., Lagoun, S., Malagon-Vina, H., Borhegyi, Z., Hauer, R., & Klausberger, T. ( 2016 ). Divisions of identified parvalbumin-expressing basket cells during working memory-guided decision making. Neuron, 91 ( 6 ), 1390 – 1401. https://doi.org/10.1016/j.neuron.2016.08.010
dc.identifier.citedreferenceLee, Y., Morrison, B. M., Li, Y., Lengacher, S., Farah, M. H., Hoffman, P. N., & Rothstein, J. D. ( 2012 ). Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature, 487 ( 7408 ), 443 – 448. https://doi.org/10.1038/nature11314
dc.identifier.citedreferenceLi, J., Han, W., Pelkey, K. A., Duan, J., Mao, X., Wang, Y. X., & Lu, W. ( 2017 ). Molecular dissection of neuroligin 2 and Slitrk3 reveals an essential framework for GABAergic synapse development. Neuron, 96 ( 4 ), 808 – 826. https://doi.org/10.1016/j.neuron.2017.10.003
dc.identifier.citedreferenceLiu, J., Dietz, K., DeLoyht, J. M., Pedre, X., Kelkar, D., Kaur, J., & Casaccia, P. ( 2012 ). Impaired adult myelination in the prefrontal cortex of socially isolated mice. Nature Neuroscience, 15 ( 12 ), 1621 – 1623. https://doi.org/10.1038/nn.3263
dc.identifier.citedreferenceLuth, H. J., Fischer, J., & Celio, M. R. ( 1992 ). Soybean lectin binding neurons in the visual cortex of the rat contain parvalbumin and are covered by glial nets. Journal of Neurocytology, 21 ( 3 ), 211 – 221. https://doi.org/10.1007/BF01194979
dc.identifier.citedreferenceMaas, D. A., Eijsink, V. D., Spoelder, M., van Hulten, J. A., De Weerd, P., Homberg, J. R., & Martens, G. J. M. ( 2020 ). Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia. Nature Communications, 11 ( 1 ), 2329. https://doi.org/10.1038/s41467-020-16218-4
dc.identifier.citedreferenceMakinodan, M., Rosen, K. M., Ito, S., & Corfas, G. ( 2012 ). A critical period for social experience-dependent oligodendrocyte maturation and myelination. Science, 337 ( 6100 ), 1357 – 1360. https://doi.org/10.1126/science.1220845
dc.identifier.citedreferenceMarques, S., Zeisel, A., Codeluppi, S., van Bruggen, D., Mendanha Falcao, A., Xiao, L., & Castelo-Branco, G. ( 2016 ). Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science, 352 ( 6291 ), 1326 – 1329. https://doi.org/10.1126/science.aaf6463
dc.identifier.citedreferenceMayer, C., Hafemeister, C., Bandler, R. C., Machold, R., Batista Brito, R., Jaglin, X., & Satija, R. ( 2018 ). Developmental diversification of cortical inhibitory interneurons. Nature, 555 ( 7697 ), 457 – 462. https://doi.org/10.1038/nature25999
dc.identifier.citedreferenceMcKenzie, I. A., Ohayon, D., Li, H., de Faria, J. P., Emery, B., Tohyama, K., & Richardson, W. D. ( 2014 ). Motor skill learning requires active central myelination. Science, 346 ( 6207 ), 318 – 322. https://doi.org/10.1126/science.1254960
dc.identifier.citedreferenceMeng, X., Kao, J. P., Lee, H. K., & Kanold, P. O. ( 2015 ). Visual deprivation causes refinement of intracortical circuits in the auditory cortex. Cell Reports, 12 ( 6 ), 955 – 964. https://doi.org/10.1016/j.celrep.2015.07.018
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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