title: Identification of different functional types of spinal afferent neurons innervating the mouse large intestine using a novel CGRPα transgenic reporter mouse.
abstract: 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-α (CGRPα)-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 CGRPα. One class expressing CGRPα 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 CGRPα and discharged tonically, with smooth, briefer action potentials and significantly greater distension sensitivity than phasically firing neurons. A third class that lacked CGRPα generated the highest-frequency firing to distension and had smaller somata. Thus, CGRPα 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 CGRPα. 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.
authors.affiliation: Discipline of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia; and.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hibberd
authors.affiliation: Discipline of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia; and.
authors.forename: Garreth R
authors.initials: GR
authors.lastname: Kestell
authors.affiliation: Discipline of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia; and.
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Kyloh
authors.affiliation: Discipline of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia; and.
authors.forename: Simon J H
authors.initials: SJ
authors.lastname: Brookes
authors.affiliation: Discipline of Surgery and Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Wattchow
authors.affiliation: Discipline of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia; and nicholas.spencer@flinders.edu.au.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Spencer
mesh_terms: D000200:Action Potentials; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D017930:Genes, Reporter; D007420:Intestine, Large / Q000166:cytology / Q000294:innervation*; D008297:Male; D051379:Mice; D009475:Neurons, Afferent / Q000145:classification / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
chemical_list: D015740:Calcitonin Gene-Related Peptide
keywords: afferent; colon; nociceptor; pain; sensory neuron