Document text
Principal Investigator: Gwenaelle S Geleoc
Organization: BOSTON CHILDREN'S HOSPITAL
Fiscal Year: 2024
Award: $538,657
Funding agency: National Institute on Deafness and Other Communication Disorders
Project summary
Hair cells of the inner ear are the primary receptors of the auditory system. They transduce mechanical
information, associated with sound waves, into electro-mechanical (outer hair cells) and electro-chemical (Inner
hair cells) signals, which lead to amplification of the initial signal and activation of afferent neuronal fibers,
respectively. While hair cells and neuronal fibers appear before birth in mice, development and maturation of
the hair cells, neurons and synapses proceeds until hearing onset, ~postnatal day 12. This process is believed to
be dynamic and modulated by hair cell activity. In particular, recent work has shown that lack of hair cell
transmission, due to absence of functional synapses or defective mechanosensation, leads to altered neuronal
maturation and specification. Successful outcomes for new therapies, including gene therapy, aimed at restoring
hair cell function after birth, may depend on restoration of auditory circuits, including mature and functional
hair cell synapses and neuronal fibers. Here we propose to assess how disruption or loss of sensory transduction
in several mouse models affects hair cell function, synaptic maturation and spiral ganglion specification.
Furthermore, we will determine if inner ear gene therapy is capable of reversing any of these observed changes
and identify the conditions for optimal recovery of auditory function. We will combine state-of-the-art
technologies to address these important questions, including high-resolution imaging, electrophysiology, single
cell RNA sequencing and localization of RNA transcripts.
Terms: <Action Potentials><Address><Affect><Afferent Neurons><Auditory><Auditory system><Birth><Brain><Brain Nervous System><Calcium><Cell Body><Cell Communication and Signaling><Cell Function><Cell Maturation><Cell Physiology><Cell Process><Cell Signaling><Cell Survival><Cell Viability><Cells><Cellular Function><Cellular Physiology><Cellular Process><Clampings><Closure by clamp><Cochlea><Cochlear Organ><Cognitive Discrimination><Corti Cell><Corti ganglion><Cortis Organ><DNA Therapy><Development><Discrimination><Electrodes><Electrophysiology><Electrophysiology (science)><Embryo><Embryonic><Encephalon><Equilibrium Hair Cell><Event><Exhibits><Exocytosis><Fiber><Fire - disasters><Fires><Gene Transfer Clinical><Genes><Genetic Intervention><Glutamates><Hair><Hair Cells><Hearing><Human><Image><Impairment><Inner Hair Cells><Inner ear hair cells><Internal Ear><Intracellular Communication and Signaling><K element><L-Glutamate><Labyrinth><Leanness><Life><Maintenance><Mechanics><Mediating><Mice><Mice Mammals><Modeling><Modern Man><Morphology><Murine><Mus><Mutant Strains Mice><Neonatal><Nerve Cells><Nerve Impulse Transmission><Nerve Transmission><Nerve Unit><Neural Cell><Neural Transmission><Neurocyte><Neuronal Transmission><Neurons><Neurophysiology / Electrophysiology><Non-Polyadenylated RNA><Organ><Organ of Corti><Outcome><Outer Hair Cells><Parturition><Patients><Pattern><Potassium><Process><Property><RNA><RNA Gene Products><Receptor Protein><Recovery><Ribonucleic Acid><Ringing-Buzzing-Tinnitus><Sampling><Sensory><Sensory Neurons><Signal Transduction><Signal Transduction Systems><Signaling><Specific qualifier value><Specified><Spiral Organ><Spiral Organ of Corti><Subcellular Process><Synapses><Synaptic><Synaptic Transmission><Synaptic ribbon><Technology><Thinness><Tinnitus><Transcript><Transduction Gene><Transmission><Vector Mediated Transfer Genes><Vesicle><Vestibular Hair Cells><Vestibular System Impairment><Vestibular defect><Vestibular dysfunction><Vestibular problems><Wild Type Mouse><Work><axon signaling><axon-glial signaling><axonal signaling><biological signal transduction><cell transduction><cellular transduction><deafness><developmental><ear hair cell><electrophysiological><fire><gene repair therapy><gene therapy><gene-based therapy><genetic hearing impairment><genetic hearing loss><genetic therapy><genomic therapy><glia signaling><glial signaling><glutamatergic><hearing in noise><hearing restoration><hereditary hearing impairment><hereditary hearing loss><high resolution imaging><imaging><inherited hearing impairment><inherited hearing loss><inner ear><inner ear development><mechanic><mechanical><mouse model><mouse mutant><murine model><nerve signaling><neural signaling><neuronal><neuronal patterning><neuronal signaling><neurotransmission><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><postnatal><postsynaptic><presynaptic><receptor><restoration><restore hearing><ribbon synapse><scRNA-seq><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><sound><speech in background noise><speech in noise><speech in speech recognition><speech recognition in noise><spiral ganglion><superresolution microscopy><synapse><synapse formation><synaptogenesis><transduced cells><transmission process><vestibular deficit><vestibular impairment><vestibular system dysfunction><voltage><wildtype mouse>