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Publication : Imaging activation of peptidergic spinal afferent varicosities within visceral organs using novel CGRPα-mCherry reporter mice.

First Author  Spencer NJ Year  2016
Journal  Am J Physiol Gastrointest Liver Physiol Volume  311
Issue  5 Pages  G880-G894
PubMed ID  27659421 Mgi Jnum  J:240466
Mgi Id  MGI:5883644 Doi  10.1152/ajpgi.00250.2016
Citation  Spencer NJ, et al. (2016) Imaging activation of peptidergic spinal afferent varicosities within visceral organs using novel CGRPalpha-mCherry reporter mice. Am J Physiol Gastrointest Liver Physiol 311(5):G880-G894
abstractText  In vertebrates, visceral pain from internal organs is detected by spinal afferents, whose cell bodies lie in dorsal root ganglia (DRG). Until now, all recordings from spinal afferents have been restricted to recording transmission of action potentials along axons, or from cell bodies lying outside their target organ, which is not where sensory transduction occurs. Our aim was to record directly from a major class of spinal afferent within visceral organs, where transduction of sensory stimuli into action potentials occurs. Using novel calcitonin gene-related peptide (CGRP)alpha reporter mice, DRG neurons expressed mCherry, including nerve axons within viscera. In colon, a minority of total CGRP immunoreactivity was attributed CGRPalpha. In isolated unstretched colon, calcium imaging from CGRPalpha-expressing varicose axons did not detect resolvable calcium transients. However, noxious levels of maintained circumferential stretch to the colon induced repetitive calcium transients simultaneously in multiple neighboring varicosities along single mCherry-expressing axons. Discrete varicosities could generate unitary calcium transients independently of neighboring varicosities. However, axons expressing mCherry only generated coordinated calcium transients when accompanied by simultaneous activation of multiple varicosities along that axon. Simultaneous imaging from different classes of myenteric neurons at the same time as mCherry-expressing axons revealed coordinated calcium transients in multiple myenteric neurons, independent of activity in mCherry-expressing axons. CGRPalpha-expressing axon terminals preferentially responded to heat, capsaicin, and low pH. We show that direct recordings can be made from the major class of peptidergic spinal afferent that contributes to visceral nociception. This approach can provide powerful insights into transduction of stimuli in viscera.
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