TY - JOUR
T1 - Mechanisms underlying auditory processing deficits in Fragile X syndrome
AU - McCullagh, Elizabeth A.
AU - Rotschafer, Sarah E.
AU - Auerbach, Benjamin D.
AU - Klug, Achim
AU - Kaczmarek, Leonard K.
AU - Cramer, Karina S.
AU - Kulesza, Randy J.
AU - Razak, Khaleel A.
AU - Lovelace, Jonathan W.
AU - Lu, Yong
AU - Koch, Ursula
AU - Wang, Yuan
N1 - Funding Information:
We would like to acknowledge our funding sources: NIH NIDCD 3T32DC012280‐05S1, FRAXA (Elizabeth A. McCullagh); Deutsche Forschungsgemeinschaft SFB665 (Ursula Koch); NIH NIDCD R01DC01919 & NS102239, FRAXA (Leonard K. Kaczmarek); NIH NIDCD R01DC010796 (Karina Cramer); NIH NIDCD R01DC017924 (Achim Klug); NIH U54 HD082008, DOD PR140683, FRAXA (Jonathan Lovelace and Khaleel Razak); NIH NIDCD R01DC016054 (Yong Lu); NIH NIDCD R01DC13074 & R21DC17267, United States‐Israel Binational Science Foundation (Yuan Wang); NIH NIDCD F32DC015160‐01A1, SFARI (Benjamin D. Auerbach).
Funding Information:
We would like to acknowledge our funding sources: NIH NIDCD 3T32DC012280-05S1, FRAXA (Elizabeth A. McCullagh); Deutsche Forschungsgemeinschaft SFB665 (Ursula Koch); NIH NIDCD R01DC01919 & NS102239, FRAXA (Leonard K. Kaczmarek); NIH NIDCD R01DC010796 (Karina Cramer); NIH NIDCD R01DC017924 (Achim Klug); NIH U54 HD082008, DOD PR140683, FRAXA (Jonathan Lovelace and Khaleel Razak); NIH NIDCD R01DC016054 (Yong Lu); NIH NIDCD R01DC13074 & R21DC17267, United States-Israel Binational Science Foundation (Yuan Wang); NIH NIDCD F32DC015160-01A1, SFARI (Benjamin D. Auerbach).
Publisher Copyright:
© 2020 Federation of American Societies for Experimental Biology
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Autism spectrum disorders (ASD) are strongly associated with auditory hypersensitivity or hyperacusis (difficulty tolerating sounds). Fragile X syndrome (FXS), the most common monogenetic cause of ASD, has emerged as a powerful gateway for exploring underlying mechanisms of hyperacusis and auditory dysfunction in ASD. This review discusses examples of disruption of the auditory pathways in FXS at molecular, synaptic, and circuit levels in animal models as well as in FXS individuals. These examples highlight the involvement of multiple mechanisms, from aberrant synaptic development and ion channel deregulation of auditory brainstem circuits, to impaired neuronal plasticity and network hyperexcitability in the auditory cortex. Though a relatively new area of research, recent discoveries have increased interest in auditory dysfunction and mechanisms underlying hyperacusis in this disorder. This rapidly growing body of data has yielded novel research directions addressing critical questions regarding the timing and possible outcomes of human therapies for auditory dysfunction in ASD.
AB - Autism spectrum disorders (ASD) are strongly associated with auditory hypersensitivity or hyperacusis (difficulty tolerating sounds). Fragile X syndrome (FXS), the most common monogenetic cause of ASD, has emerged as a powerful gateway for exploring underlying mechanisms of hyperacusis and auditory dysfunction in ASD. This review discusses examples of disruption of the auditory pathways in FXS at molecular, synaptic, and circuit levels in animal models as well as in FXS individuals. These examples highlight the involvement of multiple mechanisms, from aberrant synaptic development and ion channel deregulation of auditory brainstem circuits, to impaired neuronal plasticity and network hyperexcitability in the auditory cortex. Though a relatively new area of research, recent discoveries have increased interest in auditory dysfunction and mechanisms underlying hyperacusis in this disorder. This rapidly growing body of data has yielded novel research directions addressing critical questions regarding the timing and possible outcomes of human therapies for auditory dysfunction in ASD.
KW - Fragile X syndrome
KW - auditory system
KW - autism spectrum disorders
KW - circuit development
KW - hyperacusis
KW - synaptic transmission
UR - http://www.scopus.com/inward/record.url?scp=85079522706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079522706&partnerID=8YFLogxK
U2 - 10.1096/fj.201902435R
DO - 10.1096/fj.201902435R
M3 - Review article
C2 - 32039504
AN - SCOPUS:85079522706
SN - 0892-6638
VL - 34
SP - 3501
EP - 3518
JO - FASEB Journal
JF - FASEB Journal
IS - 3
ER -