title: Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation.
abstract: In adult animals, the neuropeptide calcitonin gene-related peptide (CGRP) is contained in cochlear efferent fibers projecting out to the cochlea, and contributes to increased suprathreshold sound-evoked activity in the adult auditory nerve. Similarly, CGRP applied to the lateral-line organ (hair cell organ) increases afferent nerve activity in adult frogs (post-metamorphic day 30), yet this increase is developmentally delayed from post-metamorphic day 4-30. In this study, we discovered that there was also a developmental delay in increased suprathreshold sound-evoked activity auditory nerve between juvenile and adult mice similar to what had been observed previously in frog. Moreover, juvenile mice with a targeted deletion of the αCGRP gene [CGRP null (-/-)] did not show a similar developmental increase in nerve activity, suggesting CGRP signaling is involved. This developmental delay is not due to a delay in CGRP expression, but instead is due to a delay in receptor formation. We observed that the increase in sound-evoked nerve activity is correlated with increased formation of cochlear CGRP receptors, which require three complexed proteins (CLR, RAMP1, RCP) to be functional. CGRP receptor formation in the cochlea was incomplete at 1 month of age (juvenile), but complete by 3 months (adult), which corresponded to the onset of suprathreshold enhancement of sound-evoked activity in wild-type animals. Taken together, these data support a model for cochlear function that is enhanced by maturation of CGRP receptor complexes.
authors.affiliation: Deptartment of Neuroscience, University of Rochester Medical Center, Rochester New York.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Dickerson
authors.affiliation: Deptartment of Biomedical Engineering, University of Rochester Medical Center, Rochester, New York.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Bussey-Gaborski
authors.affiliation: Deptartment of Otolaryngology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Holt
authors.affiliation: Deptartment of Otolaryngology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Paivi M
authors.initials: PM
authors.lastname: Jordan
authors.affiliation: Deptartment of Neuroscience, University of Rochester Medical Center, Rochester New York Deptartment of Biomedical Engineering, University of Rochester Medical Center, Rochester, New York anne_luebke@urmc.rochester.edu.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Luebke
mesh_terms: D000161:Acoustic Stimulation; D000367:Age Factors; D000818:Animals; D001309:Auditory Threshold; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D058286:Calcitonin Receptor-Like Protein / Q000378:metabolism; D003051:Cochlea / Q000254:growth & development / Q000294:innervation* / Q000378:metabolism; D003056:Cochlear Nerve / Q000254:growth & development / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem; D005838:Genotype; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D010641:Phenotype; D058262:Receptor Activity-Modifying Protein 1 / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*
chemical_list: D058286:Calcitonin Receptor-Like Protein; C545579:Calcrl protein, mouse; C491563:Crcp protein, mouse; D046912:Multiprotein Complexes; C545505:Ramp1 protein, mouse; D058262:Receptor Activity-Modifying Protein 1; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; CGRP‐RCP; CLR; RAMP1; cochlea; cochlear nerve; co‐immunoprecipitation; developmental; efferent; juvenile; lateral olivocochlear efferents; mouse; sensory coding