title: Loss of α-calcitonin gene-related peptide (αCGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR).
abstract: The neuroactive peptide calcitonin-gene related peptide (CGRP) is known to act at efferent synapses and their targets in hair cell organs, including the cochlea and lateral line. CGRP is also expressed in vestibular efferent neurons as well as a number of central vestibular neurons. Although CGRP-null (-/-) mice demonstrate a significant reduction in cochlear nerve sound-evoked activity compared with wild-type mice, it is unknown whether and how the loss of CGRP influence vestibular system function. Vestibular function was assessed by quantifying the vestibulo-ocular reflex (VOR) in alert mice. The loss of CGRP in (-/-) mice was associated with a reduction of the VOR gain of ≈50% without a concomitant change in phase. Using immunohistochemistry, we confirmed that, although CGRP staining was absent in the vestibular end-organs of null (-/-) mice, cholinergic staining appeared normal, suggesting that the overall gross development of vestibular efferent innervation was unaltered. We further confirmed that the observed deficit in vestibular function of null (-/-) mice was not the result of nontargeted effects at the level of the extraocular motor neurons and/or their innervation of extraocular muscles. Analysis of the relationship between vestibular quick phase amplitude and peak velocity revealed that extraocular motor function was unchanged, and immunohistochemistry revealed no abnormalities in motor endplates. Together, our findings show that the neurotransmitter CGRP plays a key role in ensuring VOR efficacy.
authors: Departments of Biomedical Engineering and Neurobiology & Anatomy, University of Rochester Medical Center, Rochester, New York 14642, Anne_Luebke@urmc.rochester.edu.
authors: Anne E
authors: AE
authors: Luebke
authors: Departments of Otolaryngology and Neurobiology & Anatomy, University of Rochester Medical Center, Rochester, New York 14642, and.
authors: Joseph C
authors: JC
authors: Holt
authors: Departments of Otolaryngology and Neurobiology & Anatomy, University of Rochester Medical Center, Rochester, New York 14642, and.
authors: Paivi M
authors: http://orcid.org/0000-0002-2498-5970
authors: PM
authors: Jordan
authors: Aerospace Medical Research Unit, Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada.
authors: Yi Shan
authors: YS
authors: Wong
authors: Aerospace Medical Research Unit, Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada.
authors: Jillian S
authors: JS
authors: Caldwell
authors: Aerospace Medical Research Unit, Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada.
authors: Kathleen E
authors: KE
authors: Cullen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000378:metabolism; D064032:Calbindin 2 / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency* / Q000235:genetics; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005133:Eye Movements / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D012027:Reflex, Vestibulo-Ocular / Q000235:genetics*; D014722:Vestibule, Labyrinth / Q000378:metabolism
chemical_list: D064032:Calbindin 2; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D002795:Choline O-Acetyltransferase; D019274:Botulinum Toxins, Type A; D009218:Myosins; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; efferent; mouse; sensory coding; vestibular; vestibuloocular reflex