Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation

Autor: Anne E. Luebke, Paivi M. Jordan, Joseph C. Holt, Rhiannon Bussey-Gaborski, Ian M. Dickerson
Rok vydání: 2016
Předmět:
0301 basic medicine
CLR
Physiology
Efferent
cochlea
Signalling Pathways
Receptor Activity-Modifying Protein 1
0302 clinical medicine
Integrative Physiology
CGRP
Receptor
Original Research
Mice
Knockout
integumentary system
Calcitonin Receptor-Like Protein
Age Factors
co‐immunoprecipitation
Phenotype
medicine.anatomical_structure
lateral olivocochlear efferents
CGRP‐RCP
Hair cell
cochlear nerve
medicine.medical_specialty
Mice
129 Strain
Genotype
Calcitonin Gene-Related Peptide
Biology
Calcitonin gene-related peptide
sensory coding
03 medical and health sciences
Developmental Neuroscience
Physiology (medical)
Internal medicine
Evoked Potentials
Auditory
Brain Stem
otorhinolaryngologic diseases
medicine
developmental
Animals
CGRP receptor complex
mouse
Cochlea
RAMP1
Cochlear nerve
Auditory Threshold
juvenile
030104 developmental biology
Endocrinology
Acoustic Stimulation
efferent
Multiprotein Complexes
sense organs
Sensory Neuroscience
030217 neurology & neurosurgery
Receptors
Calcitonin Gene-Related Peptide
Zdroj: Physiological Reports
ISSN: 2051-817X
DOI: 10.14814/phy2.12869
Popis: 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 α CGRP 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.
Databáze: OpenAIRE
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