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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
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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