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Publication : Identification of different functional types of spinal afferent neurons innervating the mouse large intestine using a novel CGRPα transgenic reporter mouse.

First Author  Hibberd TJ Year  2016
Journal  Am J Physiol Gastrointest Liver Physiol Volume  310
Issue  8 Pages  G561-73
PubMed ID  26822917 Mgi Jnum  J:233896
Mgi Id  MGI:5788353 Doi  10.1152/ajpgi.00462.2015
Citation  Hibberd TJ, et al. (2016) Identification of different functional types of spinal afferent neurons innervating the mouse large intestine using a novel CGRPalpha transgenic reporter mouse. Am J Physiol Gastrointest Liver Physiol 310(8):G561-73
abstractText  Spinal afferent neurons detect noxious and physiological stimuli in visceral organs. Five functional classes of afferent terminals have been extensively characterized in the colorectum, primarily from axonal recordings. Little is known about the corresponding somata of these classes of afferents, including their morphology, neurochemistry, and electrophysiology. To address this, we made intracellular recordings from somata in L6/S1 dorsal root ganglia and applied intraluminal colonic distensions. A transgenic calcitonin gene-related peptide-alpha (CGRPalpha)-mCherry reporter mouse, which enabled rapid identification of soma neurochemistry and morphology following electrophysiological recordings, was developed. Three distinct classes of low-threshold distension-sensitive colorectal afferent neurons were characterized; an additional group was distension-insensitive. Two of three low-threshold classes expressed CGRPalpha. One class expressing CGRPalpha discharged phasically, with inflections on the rising phase of their action potentials, at low frequencies, to both physiological (<30 mmHg) and noxious (>30 mmHg) distensions. The second class expressed CGRPalpha and discharged tonically, with smooth, briefer action potentials and significantly greater distension sensitivity than phasically firing neurons. A third class that lacked CGRPalpha generated the highest-frequency firing to distension and had smaller somata. Thus, CGRPalpha expression in colorectal afferents was associated with lower distension sensitivity and firing rates and larger somata, while colorectal afferents that generated the highest firing frequencies to distension had the smallest somata and lacked CGRPalpha. These data fill significant gaps in our understanding of the different classes of colorectal afferent somata that give rise to distinct functional classes of colorectal afferents. In healthy mice, the majority of sensory neurons that respond to colorectal distension are low-threshold, wide-dynamic-range afferents, encoding both physiological and noxious ranges.
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