Emergence of Functional Sensory Subtypes as Defined by Transient Receptor Potential Channel Expression

Abstract

The existence of heterogeneous populations of dorsal root ganglion (DRG) neurons conveying different somatosensory information is the basis for the perception of touch, temperature, and pain. A differential expression of transient receptor potential (TRP) cation channels contributes to this functional heterogeneity. However, little is known about the development of functionally diverse neuronal subpopulations. Here, we use calcium imaging of acutely dissociated mouse sensory neurons and quantitative reverse transcription PCR to show that TRP cation channels emerge in waves, with the diversification of functional groups starting at embryonic day 12.5 (E12.5) and extending well into the postnatal life. Functional responses of voltage-gated calcium channels were present in DRG neurons at E11.5 and reached adult levels by E14.5. Responses to capsaicin, menthol, and cinnamaldehyde were first seen at E12.5, E16.5, and postnatal day 0 (P0), when the mRNA for TRP cation channel, subfamily V, member 1 (TRPV1), TRP cation channel, subfamily M, member 8 (TRPM8), and TRP cation channel, subfamily A, member 1 (TRPA1), respectively, was first detected. Cold-sensitive neurons were present before the expression or functional responses of TRPM8 or TRPA1. Our data support a lineage relationship in which TRPM8-and TRPA1-expressing sensory neurons derive from the population of TRPV1-expressing neurons. The TRPA1 subpopulation of neurons emerges independently in two distinct classes of nociceptors: around birth in the peptidergic population and after P14 in the nonpeptidergic class. This indicates that neurons with similar receptive properties can be generated in different sublineages at different developmental stages. This study describes for the first time the emergence of functional subtypes of sensory neurons, providing new insight into the development of nociception and thermoreception.

The Rabies Virus Glycoprotein Receptor p75 NTR Is Not Essential for Rabies Virus Infection

“…First, the exposure time and the inoculum dose are supramaximal (Table 1) Neurons expressing p75 NTR are heterogeneous in size and function, and capsaicin sensitivity is a hallmark of nociceptive sensory neurons and restricted to sensory neurons expressing TRPV1 (8,9). We used ratiometric calcium imaging (8,22) on cultured cells that were vitally stained using a TRITC-tagged p75 NTR antibody directed against the extracellular domain of p75 NTR . The staining pattern reveals that both large-and small-diameter DRG cells exhibit surface expression of the receptor.…”

“…DRG neurons were studied as described previously (22). Briefly, coverslips were transferred into extracellular fluid (ECF) (145 mM NaCl, 5 mM KCl, 10 mM HEPES 10, 2 mM CaCl 2 , 1 mM MgCl 2 , 10 mM D-glucose) buffered to pH 7.4 and containing 2 M Fura-2 acetoxymethyl ester (derived from a stock solution of 2 mM Fura dissolved in dimethyl sulfoxide) and 80 M Pluronic (F-127; both from Molecular Probes) for 30 min.…”

Nociceptive sensations evoked from ‘spots’ in the skin by mild cooling and heating

“…In addition, TRPV3 continues to respond to painfully hot temperatures (Peier et al 2002b) knockout mice that lack TRPV3 show deficits in response to both noxious and innocuous heat (Moqrich et al 2005). Similarly, the menthol and cold receptor TRPM8 (McKemy et al 2002;Peier et al 2002a), which was recently shown in mice to be the principal receptor for cold below 30°C (Bautista et al 2007;Colburn et al 2007;Dhaka et al 2007;see however Munns et al 2007), has been reported in some DRG and trigeminal ganglion neurons that are capsaicin-sensitive and/or were shown to express TRPV1 (McKemy et al 2002;Okazawa et al 2004;Abe et al 2005;Xing et al 2006;Hjerling-Leffler et al 2007). (See, however, Kobayashi et al 2005.…”

Diversity in the Neural Circuitry of Cold Sensing Revealed by Genetic Axonal Labeling of Transient Receptor Potential Melastatin 8 Neurons

“…However, behavioral studies with TRPM8-null mice show that TRPM8 does serve a role in noxious cold sensing, but that it is likely not the sole determinant (Bautista et al, 2007;Colburn et al, 2007;Dhaka et al, 2007). Moreover, functional data from cultured sensory neurons show that approximately one-half of menthol-sensitive neurons are also capsaicinsensitive, suggesting coexpression of both TRPM8 and TRPV1 in this subset of cold-and menthol-sensitive neurons (McKemy et al, 2002;Viana et al, 2002;Hjerling-Leffler et al, 2007). Last, in primary culture, a subset of menthol-sensitive DRG neurons has been shown to have nociceptive properties (Xing et al, 2006).…”