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Published on: February 10, 2011
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Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation
Ian M Dickerson1, Rhiannon Bussey-Gaborski2, Joseph C Holt3
1Deptartment of Neuroscience, University of Rochester Medical Center, Rochester New York.
Physiological Reports
|July 22, 2016
Summary
Calcitonin gene-related peptide (CGRP) enhances auditory nerve activity in adult mice. This enhancement is developmentally delayed due to the maturation of CGRP receptors in the cochlea.
Area of Science:
- Neuroscience
- Auditory Physiology
- Molecular Biology
Background:
- Calcitonin gene-related peptide (CGRP) is present in cochlear efferent fibers and increases auditory nerve activity in adult animals.
- A developmental delay in CGRP's effect on nerve activity was observed in frog lateral-line organs.
- Similar developmental delays in sound-evoked auditory nerve activity were noted between juvenile and adult mice.
Purpose of the Study:
- To investigate the role of CGRP signaling in the developmental increase of suprathreshold sound-evoked activity in the auditory nerve.
- To determine the underlying mechanisms responsible for the developmental delay in auditory nerve response enhancement.
Main Methods:
- Comparison of sound-evoked auditory nerve activity in juvenile and adult wild-type mice.
- Analysis of auditory nerve activity in juvenile mice with a targeted deletion of the αCGRP gene (CGRP null).
- Assessment of CGRP receptor (CLR, RAMP1, RCP complex) formation in the cochlea at different developmental stages.
Main Results:
- Juvenile mice exhibited a developmental delay in increased suprathreshold sound-evoked auditory nerve activity compared to adults.
- CGRP null mice did not show the typical developmental increase in nerve activity, implicating CGRP signaling.
- The developmental delay was linked to delayed CGRP receptor formation, not CGRP expression, with functional receptors maturing by 3 months of age.
Conclusions:
- CGRP signaling plays a crucial role in the maturation of auditory nerve function.
- The developmental enhancement of sound-evoked activity is dependent on the maturation of functional CGRP receptor complexes in the cochlea.
- This study provides a model where cochlear function is improved by the maturation of CGRP receptor complexes.
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