Developmental hearing loss-induced perceptual deficits are rescued by genetic restoration of cortical inhibition.
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| Title: | Developmental hearing loss-induced perceptual deficits are rescued by genetic restoration of cortical inhibition. |
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| Authors: | Masri, Samer1 samer@nyu.edu, Mowery, Todd M.2, Fair, Regan1, Sanes, Dan H.1,3,4,5 |
| Source: | Proceedings of the National Academy of Sciences of the United States of America. 6/11/2024, Vol. 121 Issue 24, p1-10. 22p. |
| Subjects: | Inhibitory postsynaptic potential, Auditory cortex, Pyramidal neurons, Genetic vectors, Speech perception, Curcumin |
| Abstract: | Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAA and metabotropic GABAB receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAA receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABAA, Gabra1; GABAB, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABAB receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABAB receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders. [ABSTRACT FROM AUTHOR] |
| Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 177939331 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Developmental hearing loss-induced perceptual deficits are rescued by genetic restoration of cortical inhibition. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Masri%2C+Samer%22">Masri, Samer</searchLink><relatesTo>1</relatesTo><i> samer@nyu.edu</i><br /><searchLink fieldCode="AR" term="%22Mowery%2C+Todd+M%2E%22">Mowery, Todd M.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Fair%2C+Regan%22">Fair, Regan</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Sanes%2C+Dan+H%2E%22">Sanes, Dan H.</searchLink><relatesTo>1,3,4,5</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink>. 6/11/2024, Vol. 121 Issue 24, p1-10. 22p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Inhibitory+postsynaptic+potential%22">Inhibitory postsynaptic potential</searchLink><br /><searchLink fieldCode="DE" term="%22Auditory+cortex%22">Auditory cortex</searchLink><br /><searchLink fieldCode="DE" term="%22Pyramidal+neurons%22">Pyramidal neurons</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+vectors%22">Genetic vectors</searchLink><br /><searchLink fieldCode="DE" term="%22Speech+perception%22">Speech perception</searchLink><br /><searchLink fieldCode="DE" term="%22Curcumin%22">Curcumin</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAA and metabotropic GABAB receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAA receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABAA, Gabra1; GABAB, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABAB receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABAB receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1073/pnas.2311570121 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 22 StartPage: 1 Subjects: – SubjectFull: Inhibitory postsynaptic potential Type: general – SubjectFull: Auditory cortex Type: general – SubjectFull: Pyramidal neurons Type: general – SubjectFull: Genetic vectors Type: general – SubjectFull: Speech perception Type: general – SubjectFull: Curcumin Type: general Titles: – TitleFull: Developmental hearing loss-induced perceptual deficits are rescued by genetic restoration of cortical inhibition. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Masri, Samer – PersonEntity: Name: NameFull: Mowery, Todd M. – PersonEntity: Name: NameFull: Fair, Regan – PersonEntity: Name: NameFull: Sanes, Dan H. IsPartOfRelationships: – BibEntity: Dates: – D: 11 M: 06 Text: 6/11/2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 00278424 Numbering: – Type: volume Value: 121 – Type: issue Value: 24 Titles: – TitleFull: Proceedings of the National Academy of Sciences of the United States of America Type: main |
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