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Visualizing cold spots: TRPM8-expressing sensory neurons and their projections.
J Neurosci. 2008 Jan 16; 28(3):566-75.JN

Abstract

Environmental stimuli such as temperature and pressure are sensed by dorsal root ganglion (DRG) neurons. DRG neurons are heterogeneous, but molecular markers that identify unique functional subpopulations are mainly lacking. ThermoTRPs are members of the transient receptor potential family of ion channels and are gated by shifts in temperature. TRPM8 is activated by cooling, and TRPM8-deficient mice have severe deficits in cool thermosensation. The anatomical and functional properties of TRPM8-expressing fibers have not been not comprehensively investigated. We use mice engineered to express the farnesylated enhanced green fluorescent protein (EGFPf) from the TRPM8 locus (TRPM8(EGFPf)) to explore this issue. Virtually all EGFPf-positive cultured DRG neurons from hemizygous mice (TRPM8(EGFPf/+)) responded to cold and menthol. In contrast, EGFPf-positive DRGs from homozygous mice (TRPM8(EGFPf/EGFPf)) had drastically reduced cold responses and no menthol responses. In vivo, EGFPf-positive neurons marked a unique population of DRG neurons, a majority of which do not coexpress nociceptive markers. The fraction of DRG neurons expressing EGFPf was not altered under an inflammatory condition, although an increase in TRPV1-coexpressing neurons was observed. TRPM8(EGFPf) neurons project to the superficial layer I of the spinal cord, making distinct contacts when compared with peptidergic projections. At the periphery, TRPM8(EGFPf) projections mark unique endings in the most superficial layers of epidermis, including bush/cluster endings of the mystacial pads. We show that TRPM8 expression functionally associates with cold sensitivity in cultured DRGs, and provide the first glimpses of the unique anatomical architecture of cold fibers in vivo.

Authors+Show Affiliations

Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18199758

Citation

Dhaka, Ajay, et al. "Visualizing Cold Spots: TRPM8-expressing Sensory Neurons and Their Projections." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 28, no. 3, 2008, pp. 566-75.
Dhaka A, Earley TJ, Watson J, et al. Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J Neurosci. 2008;28(3):566-75.
Dhaka, A., Earley, T. J., Watson, J., & Patapoutian, A. (2008). Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 28(3), 566-75. https://doi.org/10.1523/JNEUROSCI.3976-07.2008
Dhaka A, et al. Visualizing Cold Spots: TRPM8-expressing Sensory Neurons and Their Projections. J Neurosci. 2008 Jan 16;28(3):566-75. PubMed PMID: 18199758.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. AU - Dhaka,Ajay, AU - Earley,Taryn J, AU - Watson,James, AU - Patapoutian,Ardem, PY - 2008/1/18/pubmed PY - 2008/2/9/medline PY - 2008/1/18/entrez SP - 566 EP - 75 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 28 IS - 3 N2 - Environmental stimuli such as temperature and pressure are sensed by dorsal root ganglion (DRG) neurons. DRG neurons are heterogeneous, but molecular markers that identify unique functional subpopulations are mainly lacking. ThermoTRPs are members of the transient receptor potential family of ion channels and are gated by shifts in temperature. TRPM8 is activated by cooling, and TRPM8-deficient mice have severe deficits in cool thermosensation. The anatomical and functional properties of TRPM8-expressing fibers have not been not comprehensively investigated. We use mice engineered to express the farnesylated enhanced green fluorescent protein (EGFPf) from the TRPM8 locus (TRPM8(EGFPf)) to explore this issue. Virtually all EGFPf-positive cultured DRG neurons from hemizygous mice (TRPM8(EGFPf/+)) responded to cold and menthol. In contrast, EGFPf-positive DRGs from homozygous mice (TRPM8(EGFPf/EGFPf)) had drastically reduced cold responses and no menthol responses. In vivo, EGFPf-positive neurons marked a unique population of DRG neurons, a majority of which do not coexpress nociceptive markers. The fraction of DRG neurons expressing EGFPf was not altered under an inflammatory condition, although an increase in TRPV1-coexpressing neurons was observed. TRPM8(EGFPf) neurons project to the superficial layer I of the spinal cord, making distinct contacts when compared with peptidergic projections. At the periphery, TRPM8(EGFPf) projections mark unique endings in the most superficial layers of epidermis, including bush/cluster endings of the mystacial pads. We show that TRPM8 expression functionally associates with cold sensitivity in cultured DRGs, and provide the first glimpses of the unique anatomical architecture of cold fibers in vivo. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/18199758/Visualizing_cold_spots:_TRPM8_expressing_sensory_neurons_and_their_projections_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=18199758 DB - PRIME DP - Unbound Medicine ER -