TY - JOUR
T1 - Transmission disrupted
T2 - Modeling auditory synaptopathy in zebrafish
AU - Kindt, Katie S.
AU - Sheets, Lavinia
N1 - Publisher Copyright:
© 2018 Kindt and Sheets.
PY - 2018/9/11
Y1 - 2018/9/11
N2 - Sensorineural hearing loss is the most common form of hearing loss in humans, and results from either dysfunction in hair cells, the sensory receptors of sound, or the neurons that innervate hair cells. A specific type of sensorineural hearing loss, referred to as auditory synaptopathy, occurs when hair cells are able to detect sound but fail to transmit sound stimuli at the hair-cell synapse. Auditory synaptopathy can originate from genetic alterations that specifically disrupt hair-cell synapse function. Additionally, environmental factors such as noise exposure can leave hair cells intact but result in loss of hair-cell synapses, and represent an acquired form of auditory synaptopathy. The zebrafish model has emerged as a valuable system for studies of hair-cell function, and specifically hair-cell synaptopathy. In this review, we describe the experimental tools that have been developed to study hair-cell synapses in zebrafish. We discuss how zebrafish genetics has helped identify and define the roles of hair-cell synaptic proteins crucial for hearing in humans, and highlight how studies in zebrafish have contributed to our understanding of hair-cell synapse formation and function. In addition, we also discuss work that has used noise exposure or pharmacological mimic of noise-induced excitotoxicity in zebrafish to define cellular mechanisms underlying noise-induced hair-cell damage and synapse loss. Lastly, we highlight how future studies in zebrafish could enhance our understanding of the pathological processes underlying synapse loss in both genetic and acquired auditory synaptopathy. This knowledge is critical in order to develop therapies that protect or repair auditory synaptic contacts.
AB - Sensorineural hearing loss is the most common form of hearing loss in humans, and results from either dysfunction in hair cells, the sensory receptors of sound, or the neurons that innervate hair cells. A specific type of sensorineural hearing loss, referred to as auditory synaptopathy, occurs when hair cells are able to detect sound but fail to transmit sound stimuli at the hair-cell synapse. Auditory synaptopathy can originate from genetic alterations that specifically disrupt hair-cell synapse function. Additionally, environmental factors such as noise exposure can leave hair cells intact but result in loss of hair-cell synapses, and represent an acquired form of auditory synaptopathy. The zebrafish model has emerged as a valuable system for studies of hair-cell function, and specifically hair-cell synaptopathy. In this review, we describe the experimental tools that have been developed to study hair-cell synapses in zebrafish. We discuss how zebrafish genetics has helped identify and define the roles of hair-cell synaptic proteins crucial for hearing in humans, and highlight how studies in zebrafish have contributed to our understanding of hair-cell synapse formation and function. In addition, we also discuss work that has used noise exposure or pharmacological mimic of noise-induced excitotoxicity in zebrafish to define cellular mechanisms underlying noise-induced hair-cell damage and synapse loss. Lastly, we highlight how future studies in zebrafish could enhance our understanding of the pathological processes underlying synapse loss in both genetic and acquired auditory synaptopathy. This knowledge is critical in order to develop therapies that protect or repair auditory synaptic contacts.
KW - Deafness/hearing loss
KW - Hair cells (HCs)
KW - Ribbon synapse
KW - Synaptic transmission
KW - Zebrafish model system
UR - http://www.scopus.com/inward/record.url?scp=85053722124&partnerID=8YFLogxK
U2 - 10.3389/fcell.2018.00114
DO - 10.3389/fcell.2018.00114
M3 - Review article
C2 - 30258843
AN - SCOPUS:85053722124
SN - 2296-634X
VL - 6
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
IS - SEP
M1 - 114
ER -