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Seminar Series: Calcitonin Gene Related Peptide’s (CGRP’s) Role in Auditory and Vestibular Efferent Feedback and Migraine

Dr. Anne Luebke, Associate Professor of Biomedical Engineering and Neurobiology & Anatomy, University of Rochester

River Campus, Robert B. Goergen Hall, Sloan Auditorium (Room 101)

In adult animals, the neurotransmitter calcitonin gene-related peptide (CGRP) is released from cochlear efferent fibers causing increased suprathreshold sound-evoked activity in the cochlear nerve.  We discovered a developmental delay in CGRP-mediated detection of sound in between juvenile to adult mice, and determined that the formation of functional CGRP receptors (a complex of CLR, RAMP1, RCP) increased during development from juvenile to adult which could be a cause of this delay.

CGRP is also expressed in vestibular efferent neurons, yet it is unknown whether and how the loss of CGRP influences vestibular system function.   We investigated vestibular function by quantifying the vestibulo-ocular reflex (VOR) in alert adult mice and found that the loss of CGRP in null (-/-) mice was associated with a reduction of the VOR gain of ≈50% without a concomitant change in phase.

While the loss of CGRP causes auditory and vestibular deficits, there are new studies showing that increases in CGRP play a role in sensory hypersensitivity found in migraine; i) CGRP levels are elevated during migraine, ii) normalization of CGRP levels is associated with the relief of pain by triptan anti-migraine drugs, and iii) injected CGRP triggers migraines in migraineurs, but not in subjects who do not normally get migraines.  We will introduce experiments in the CGRP-sensitized mouse that contains elevated CGRP receptors, as a mouse model of migraine.