Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome

Fragile X (FX) syndrome is one of the leading inherited causes of autism spectrum disorder (ASD). A majority of FX and ASD patients exhibit sensory hypersensitivity, including auditory hypersensitivity or hyperacusis, a condition in which everyday sounds are perceived as much louder than normal. Aud...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Benjamin D. Auerbach, Senthilvelan Manohar, Kelly Radziwon, Richard Salvi
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Autism spectrum disorder Fragile X Auditory hypersensitivity Hyperacusis Temporal integration Metabotropic glutamate receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/5c56de3d694d4586bf36dc13c0017d0f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5c56de3d694d4586bf36dc13c0017d0f
record_format	dspace
spelling	oai:doaj.org-article:5c56de3d694d4586bf36dc13c0017d0f2021-12-04T04:33:09ZAuditory hypersensitivity and processing deficits in a rat model of fragile X syndrome1095-953X10.1016/j.nbd.2021.105541https://doaj.org/article/5c56de3d694d4586bf36dc13c0017d0f2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0969996121002904https://doaj.org/toc/1095-953XFragile X (FX) syndrome is one of the leading inherited causes of autism spectrum disorder (ASD). A majority of FX and ASD patients exhibit sensory hypersensitivity, including auditory hypersensitivity or hyperacusis, a condition in which everyday sounds are perceived as much louder than normal. Auditory processing deficits in FX and ASD also afford the opportunity to develop objective and quantifiable outcome measures that are likely to translate between humans and animal models due to the well-conserved nature of the auditory system and well-developed behavioral read-outs of sound perception. Therefore, in this study we characterized auditory hypersensitivity in a Fmr1 knockout (KO) transgenic rat model of FX using an operant conditioning task to assess sound detection thresholds and suprathreshold auditory reaction time-intensity (RT-I) functions, a reliable psychoacoustic measure of loudness growth, at a variety of stimulus frequencies, bandwidths, and durations. Male Fmr1 KO and littermate WT rats both learned the task at the same rate and exhibited normal hearing thresholds. However, Fmr1 KO rats had faster auditory RTs over a broad range of intensities and steeper RT-I slopes than WT controls, perceptual evidence of excessive loudness growth in Fmr1 KO rats. Furthermore, we found that Fmr1 KO animals exhibited abnormal perceptual integration of sound duration and bandwidth, with diminished temporal but enhanced spectral integration of sound intensity. Because temporal and spectral integration of sound stimuli were altered in opposite directions in Fmr1 KO rats, this suggests that abnormal RTs in these animals are evidence of aberrant auditory processing rather than generalized hyperactivity or altered motor responses. Together, these results are indicative of fundamental changes to low-level auditory processing in Fmr1 KO animals. Finally, we demonstrated that antagonism of metabotropic glutamate receptor 5 (mGlu5) selectively and dose-dependently restored normal loudness growth in Fmr1 KO rats, suggesting a pharmacologic approach for alleviating sensory hypersensitivity associated with FX. This study leverages the tractable nature of the auditory system and the unique behavioral advantages of rats to provide important insights into the nature of a centrally important yet understudied aspect of FX and ASD.Benjamin D. AuerbachSenthilvelan ManoharKelly RadziwonRichard SalviElsevierarticleAutism spectrum disorderFragile XAuditory hypersensitivityHyperacusisTemporal integrationMetabotropic glutamate receptorNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeurobiology of Disease, Vol 161, Iss , Pp 105541- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Autism spectrum disorder Fragile X Auditory hypersensitivity Hyperacusis Temporal integration Metabotropic glutamate receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Autism spectrum disorder Fragile X Auditory hypersensitivity Hyperacusis Temporal integration Metabotropic glutamate receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Benjamin D. Auerbach Senthilvelan Manohar Kelly Radziwon Richard Salvi Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome
description	Fragile X (FX) syndrome is one of the leading inherited causes of autism spectrum disorder (ASD). A majority of FX and ASD patients exhibit sensory hypersensitivity, including auditory hypersensitivity or hyperacusis, a condition in which everyday sounds are perceived as much louder than normal. Auditory processing deficits in FX and ASD also afford the opportunity to develop objective and quantifiable outcome measures that are likely to translate between humans and animal models due to the well-conserved nature of the auditory system and well-developed behavioral read-outs of sound perception. Therefore, in this study we characterized auditory hypersensitivity in a Fmr1 knockout (KO) transgenic rat model of FX using an operant conditioning task to assess sound detection thresholds and suprathreshold auditory reaction time-intensity (RT-I) functions, a reliable psychoacoustic measure of loudness growth, at a variety of stimulus frequencies, bandwidths, and durations. Male Fmr1 KO and littermate WT rats both learned the task at the same rate and exhibited normal hearing thresholds. However, Fmr1 KO rats had faster auditory RTs over a broad range of intensities and steeper RT-I slopes than WT controls, perceptual evidence of excessive loudness growth in Fmr1 KO rats. Furthermore, we found that Fmr1 KO animals exhibited abnormal perceptual integration of sound duration and bandwidth, with diminished temporal but enhanced spectral integration of sound intensity. Because temporal and spectral integration of sound stimuli were altered in opposite directions in Fmr1 KO rats, this suggests that abnormal RTs in these animals are evidence of aberrant auditory processing rather than generalized hyperactivity or altered motor responses. Together, these results are indicative of fundamental changes to low-level auditory processing in Fmr1 KO animals. Finally, we demonstrated that antagonism of metabotropic glutamate receptor 5 (mGlu5) selectively and dose-dependently restored normal loudness growth in Fmr1 KO rats, suggesting a pharmacologic approach for alleviating sensory hypersensitivity associated with FX. This study leverages the tractable nature of the auditory system and the unique behavioral advantages of rats to provide important insights into the nature of a centrally important yet understudied aspect of FX and ASD.
format	article
author	Benjamin D. Auerbach Senthilvelan Manohar Kelly Radziwon Richard Salvi
author_facet	Benjamin D. Auerbach Senthilvelan Manohar Kelly Radziwon Richard Salvi
author_sort	Benjamin D. Auerbach
title	Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome
title_short	Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome
title_full	Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome
title_fullStr	Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome
title_full_unstemmed	Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome
title_sort	auditory hypersensitivity and processing deficits in a rat model of fragile x syndrome
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5c56de3d694d4586bf36dc13c0017d0f
work_keys_str_mv	AT benjamindauerbach auditoryhypersensitivityandprocessingdeficitsinaratmodeloffragilexsyndrome AT senthilvelanmanohar auditoryhypersensitivityandprocessingdeficitsinaratmodeloffragilexsyndrome AT kellyradziwon auditoryhypersensitivityandprocessingdeficitsinaratmodeloffragilexsyndrome AT richardsalvi auditoryhypersensitivityandprocessingdeficitsinaratmodeloffragilexsyndrome
_version_	1718373032340226048

Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome

Ejemplares similares