| Autor: |
O'Connor AP; School of Biosciences, University of Sheffield, Sheffield, United Kingdom., Amariutei AE; School of Biosciences, University of Sheffield, Sheffield, United Kingdom., Zanella A; School of Biosciences, University of Sheffield, Sheffield, United Kingdom., Hool SA; School of Biosciences, University of Sheffield, Sheffield, United Kingdom., Carlton AJ; School of Biosciences, University of Sheffield, Sheffield, United Kingdom., Kong F; School of Biosciences, University of Sheffield, Sheffield, United Kingdom., Saenz-Roldan M; Université Paris Cité, Institut Pasteur, AP-HP, INSERM, Fondation Pour l'Audition, Institut de l'Audition, IHU reConnect, F-75012 Paris, France., Jeng JY; School of Biosciences, University of Sheffield, Sheffield, United Kingdom., Lecomte MJ; Université Paris Cité, Institut Pasteur, AP-HP, INSERM, Fondation Pour l'Audition, Institut de l'Audition, IHU reConnect, F-75012 Paris, France., Johnson SL; School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom., Safieddine S; Université Paris Cité, Institut Pasteur, AP-HP, INSERM, Fondation Pour l'Audition, Institut de l'Audition, IHU reConnect, F-75012 Paris, France., Marcotti W; School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom. |
| Abstrakt: |
In the mammalian cochlea, sensory hair cells are crucial for the transduction of acoustic stimuli into electrical signals, which are then relayed to the central auditory pathway via spiral ganglion neuron (SGN) afferent dendrites. The SGN output is directly modulated by inhibitory cholinergic axodendritic synapses from the efferent fibers originating in the superior olivary complex. When the adult cochlea is subjected to noxious stimuli or aging, the efferent system undergoes major rewiring, such that it reestablishes direct axosomatic contacts with the inner hair cells (IHCs), which occur only transiently during prehearing stages of development. The trigger, origin, and degree of efferent plasticity in the cochlea remains largely unknown. Using functional and morphological approaches, we demonstrate that efferent plasticity in the adult cochlea occurs as a direct consequence of mechanoelectrical transducer current dysfunction. We also show that, different from prehearing stages of development, the lateral olivocochlear - but not the medial olivocochlear - efferent fibers are those that form the axosomatic synapses with the IHCs. The study also demonstrates that in vivo restoration of IHC function using AAV-Myo7a rescue reestablishes the synaptic profile of adult IHCs and improves hearing, highlighting the potential of using gene-replacement therapy for progressive hearing loss. |
