title: Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons.
abstract: During nervous system development, critical periods are usually defined as early periods during which manipulations dramatically change neuronal structure or function, whereas the same manipulations in mature animals have little or no effect on the same property. Neurons in the ventral cochlear nucleus (CN) are dependent on excitatory afferent input for survival during a critical period of development. Cochlear removal in young mammals and birds results in rapid death of target neurons in the CN. Cochlear removal in older animals results in little or no neuron death. However, the extent to which hair-cell-specific afferent activity prevents neuronal death in the neonatal brain is unknown. We further explore this phenomenon using a new mouse model that allows temporal control of cochlear hair cell deletion. Hair cells express the human diphtheria toxin (DT) receptor behind the Pou4f3 promoter. Injections of DT resulted in nearly complete loss of organ of Corti hair cells within 1 week of injection regardless of the age of injection. Injection of DT did not influence surrounding supporting cells directly in the sensory epithelium or spiral ganglion neurons (SGNs). Loss of hair cells in neonates resulted in rapid and profound neuronal loss in the ventral CN, but not when hair cells were eliminated at a more mature age. In addition, normal survival of SGNs was dependent on hair cell integrity early in development and less so in mature animals. This defines a previously undocumented critical period for SGN survival.
authors.affiliation: Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery.
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.affiliation: Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Strong
authors.affiliation: Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Tejbeer
authors.initials: T
authors.lastname: Kaur
authors.affiliation: Discapacidades Neurológicas and School of medicine, Universidad de Castilla-La Mancha, 02008 Albacete, Spain, and.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Juiz
authors.affiliation: Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Oesterle
authors.affiliation: Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery.
authors.forename: Clifford
authors.initials: C
authors.lastname: Hume
authors.affiliation: Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Warchol
authors.affiliation: Department of Biochemistry and Howard Hughes Medical Institute, and.
authors.forename: Richard D
authors.identifier: http://orcid.org/0000-0001-6587-0582
authors.initials: RD
authors.lastname: Palmiter
authors.affiliation: Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, rubel@uw.edu.
authors.forename: Edwin W
authors.identifier: http://orcid.org/0000-0002-7265-0411
authors.initials: EW
authors.lastname: Rubel
mesh_terms: D000818:Animals; D016923:Cell Death; D017626:Cochlear Nucleus / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D004167:Diphtheria Toxin / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006309:Hearing; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013136:Spiral Ganglion / Q000166:cytology / Q000254:growth & development* / Q000502:physiology
chemical_list: D004167:Diphtheria Toxin; D066257:Heparin-binding EGF-like Growth Factor
keywords: cochlea; cochlear nucleus; critical period; diphtheria toxin receptor knock-in; neuronal death; spiral ganglion