Piccolino is required for ribbon architecture at cochlear inner hair cell synapses and for hearing.
Susann MichanskiRohan KapoorAnna Maria SteyerWiebke MöbiusIris FrüholzFrauke AckermannMehmet GültasCraig C GarnerF Kent HamraJakob NeefNicola StrenzkeTobias MoserCarolin WichmannPublished in: EMBO reports (2023)
Cochlear inner hair cells (IHCs) form specialized ribbon synapses with spiral ganglion neurons that tirelessly transmit sound information at high rates over long time periods with extreme temporal precision. This functional specialization is essential for sound encoding and is attributed to a distinct molecular machinery with unique players or splice variants compared to conventional neuronal synapses. Among these is the active zone (AZ) scaffold protein piccolo/aczonin, which is represented by its short splice variant piccolino at cochlear and retinal ribbon synapses. While the function of piccolo at synapses of the central nervous system has been intensively investigated, the role of piccolino at IHC synapses remains unclear. In this study, we characterize the structure and function of IHC synapses in piccolo gene-trap mutant rats (Pclo gt/gt ). We find a mild hearing deficit with elevated thresholds and reduced amplitudes of auditory brainstem responses. Ca 2+ channel distribution and ribbon morphology are altered in apical IHCs, while their presynaptic function seems to be unchanged. We conclude that piccolino contributes to the AZ organization in IHCs and is essential for normal hearing.
Keyphrases
- hearing loss
- copy number
- oxidative stress
- climate change
- diabetic retinopathy
- gene expression
- genome wide
- brain injury
- cell death
- atomic force microscopy
- cell cycle arrest
- optical coherence tomography
- mesenchymal stem cells
- bone marrow
- small molecule
- health information
- transcription factor
- cerebrospinal fluid
- optic nerve
- pi k akt