ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Adenomatous Polyposis Coli Protein Deletion in Efferent Olivocochlear Neurons Perturbs Afferent Synaptic Maturation and Reduces the Dynamic Range of Hearing.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Nuclear Translocation Triggered at the Onset of Hearing in Cochlear Inner Hair Cells of Rats and Mice.Journal of the Association for Research in Otolaryngology : JARO · 2023Article
- Synaptic activity is not required for establishing heterogeneity of inner hair cell ribbon synapses.Frontiers in molecular neuroscience · 2023Article
- Low-voltage Activating KExperimental neurobiology · 2022Article
- Altered neural networks and cognition in a hereditary colon cancer.IBRO neuroscience reports · 2021Article
- Generation and characterization of a P2rx2 V60L mouse model for DFNA41.Human molecular genetics · 2021Article
- Deletion of BDNF in Pax2 Lineage-Derived Interneuron Precursors in the Hindbrain Hampers the Proportion of Excitation/Inhibition, Learning, and Behavior.Frontiers in molecular neuroscience · 2021Article
- Striatin Is Required for Hearing and Affects Inner Hair Cells and Ribbon Synapses.Frontiers in cell and developmental biology · 2020Article
- Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3.Scientific reports · 2019Article
- Talking back: Development of the olivocochlear efferent system.Wiley interdisciplinary reviews. Developmental biology · 2018Review
- Spatial Gradients in the Size of Inner Hair Cell Ribbons Emerge Before the Onset of Hearing in Rats.Journal of the Association for Research in Otolaryngology : JARO · 2017Article
- Chronic Oxidative Stress, Mitochondrial Dysfunction, Nrf2 Activation and Inflammation in the Hippocampus Accompany Heightened Systemic Inflammation and Oxidative Stress in an Animal Model of Gulf War Illness.Frontiers in molecular neuroscience · 2017Article
- Activity-Dependent Phosphorylation by CaMKIIδ Alters the CaFrontiers in synaptic neuroscience · 2017Article
- Minimal Effects of Age and Exposure to a Noisy Environment on Hearing in Alpha9 Nicotinic Receptor Knockout Mice.Frontiers in neuroscience · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Normal hearing requires proper differentiation of afferent ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) that carry acoustic information to the brain. Within individual IHCs, presynaptic ribbons show a size gradient with larger ribbons on the modiolar face and smaller ribbons on the pillar face. This structural gradient is associated with a gradient of spontaneous rates and threshold sensitivity, which is essential for a wide dynamic range of hearing. Despite their importance for hearing, mechanisms that direct ribbon differentiation are poorly defined. We recently identified adenomatous polyposis coli protein (APC) as a key regulator of interneuronal synapse maturation. Here, we show that APC is required for ribbon size heterogeneity and normal cochlear function. Compared with wild-type littermates, APC conditional knock-out (cKO) mice exhibit decreased auditory brainstem responses. The IHC ribbon size gradient is also perturbed. Whereas the normal-developing IHCs display ribbon size gradients before hearing onset, ribbon sizes are aberrant in APC cKOs from neonatal ages on. Reporter expression studies show that the CaMKII-Cre used to delete the floxed APC gene is present in efferent olivocochlear (OC) neurons, not IHCs or SGNs. APC loss led to increased volumes and numbers of OC inhibitory dopaminergic boutons on neonatal SGN fibers. Our findings identify APC in efferent OC neurons as essential for regulating ribbon heterogeneity, dopaminergic terminal differentiation, and cochlear sensitivity. This APC effect on auditory epithelial cell synapses resembles interneuronal and nerve-muscle synapses, thereby defining a global role for APC in synaptic maturation in diverse cell types. SIGNIFICANCE STATEMENT: This study identifies novel molecules and cellular interactions that are essential for the proper maturation of afferent ribbon synapses in sensory cells of the inner ear, and for normal hearing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.