Abstract

All hair cell systems, including lateral-line organs, vestibular organs and the cochlea, contain an efferent innervations, originating in the brainstem and projecting to the hair cells and/or neural elements in the sensory epithelium. In the mammalian cochlea, this efferent system originates in the superior olivary complex and has been called the olivocochlear (OC) pathway and consists of a medial (MOC) and lateral (LOC) component. Cochlear efferent is likely to serve two functions: protection from acoustic over stimulation and enhancement of sound recognition in the presence of background noises. In the last project period, we determined that the MOC efferent could protect the cochlea from acoustic over stimulation working through the newly discovered alpha 9/10 nACh receptor complex. In this next project period, we will focus on the LOC efferent fibers that contain calcitonin gene-related peptide (CGRP). We determined that the loss of CGRP in knockout mice reduced sound-evoked activity of the cochlear nerve, which would then cause a reduction in the dynamic range of sound perception. However there are several CGRP-ergic neuronal systems in hair cell organs: the efferent as well as pathways innervating the vasculature, which could have contributed to the auditory phenotype. Our goal is to determine the molecular mechanism by which CGRP released from efferent fibers influences neuronal afferents. In these aims we will (1) determine effect of CGRP receptor signaling on sound-evoked activity; (2) determine biochemical time course for CGRP receptor signaling; (3) determine physiological target cells for CGRP receptor signaling. We will use adenoviral gene transfer, DPOAE, ABR, and CAP testing for auditory function, immunohistochemisty, coimmunoprecipitation, biolistic transfection, and FRET imaging to carry out these aims. Information gained from these studies will provide direct assessment of the molecular mechanisms used by the CGRP efferent feedback pathway to enhance sound-evoked activity in the cochlear nerve. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003086-12
Application #
7268804
Study Section
Auditory System Study Section (AUD)
Program Officer
Watson, Bracie
Project Start
1996-09-30
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
12
Fiscal Year
2007
Total Cost
$336,511
Indirect Cost

  Institution

Name
University of Rochester
Department
Neurosciences
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Walton, Joseph P; Dziorny, Adam C; Vasilyeva, Olga N et al. (2018) Loss of the Cochlear Amplifier Prestin Reduces Temporal Processing Efficacy in the Central Auditory System. Front Cell Neurosci 12:291
Dickerson, Ian M; Bussey-Gaborski, Rhiannon; Holt, Joseph C et al. (2016) Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation. Physiol Rep 4:
Safe, Theresa M; Luebke, Anne E (2016) Prenatal low dosage dioxin (TCDD) exposure impairs cochlear function resulting in auditory neuropathy. Hear Res 331:7-12
Luebke, Anne E; Stagner, Barden B; Martin, Glen K et al. (2015) Influence of sound-conditioning on noise-induced susceptibility of distortion-product otoacoustic emissions. J Acoust Soc Am 138:58-64
Luebke, Anne E; Holt, Joseph C; Jordan, Paivi M et al. (2014) Loss of ?-calcitonin gene-related peptide (?CGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR). J Neurosci 34:10453-8
Luebke, Anne E; Stagner, Barden B; Martin, Glen K et al. (2014) Adaptation of distortion product otoacoustic emissions predicts susceptibility to acoustic over-exposure in alert rabbits. J Acoust Soc Am 135:1941-9
Mihaila, Camelia; Schramm, Jordan; Strathmann, Frederick G et al. (2011) Identifying a window of vulnerability during fetal development in a maternal iron restriction model. PLoS One 6:e17483
Bogart, L J; Levy, A D; Gladstone, M et al. (2011) Loss of prestin does not alter the development of auditory cortical dendritic spines. Neural Plast 2011:305621
Polesskaya, Oksana; Cunningham, Lisa L; Francis, Shimon P et al. (2010) Ablation of mixed lineage kinase 3 (Mlk3) does not inhibit ototoxicity induced by acoustic trauma or aminoglycoside exposure. Hear Res 270:21-7
Luebke, Anne E; Rova, Cherokee; Von Doersten, Peter G et al. (2009) Adenoviral and AAV-mediated gene transfer to the inner ear: role of serotype, promoter, and viral load on in vivo and in vitro infection efficiencies. Adv Otorhinolaryngol 66:87-98

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