QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 16, 2008, 28(3):566-575; doi:10.1523/JNEUROSCI.3976-07.2008

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Dhaka, A. Articles by Patapoutian, A. Search for Related Content PubMed PubMed Citation Articles by Dhaka, A. Articles by Patapoutian, A.

 Previous Article  |  Next Article 

Cellular/Molecular
Visualizing Cold Spots: TRPM8-Expressing Sensory Neurons and Their Projections

Ajay Dhaka,¹ Taryn J. Earley,¹ James Watson,² and Ardem Patapoutian^1,2

¹Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, and ²Genomics Institute of the Novartis Research Foundation, San Diego, California 92121

Correspondence should be addressed to Ardem Patapoutian, Department of Cell Biology, ICND202, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Email: apatapou{at}gnf.org

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.

Key words: TRPM8; ThermoTRP; DRG; thermosensation; cold; pain

---

Received Aug. 30, 2007; revised Nov. 13, 2007; accepted Nov. 30, 2007.

Correspondence should be addressed to Ardem Patapoutian, Department of Cell Biology, ICND202, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Email: apatapou{at}gnf.org

This article has been cited by other articles:

				Y. Karashima, K. Talavera, W. Everaerts, A. Janssens, K. Y. Kwan, R. Vennekens, B. Nilius, and T. Voets TRPA1 acts as a cold sensor in vitro and in vivo PNAS, January 27, 2009; 106(4): 1273 - 1278. [Abstract] [Full Text] [PDF]

				R. L. Daniels, Y. Takashima, and D. D. McKemy Activity of the Neuronal Cold Sensor TRPM8 Is Regulated by Phospholipase C via the Phospholipid Phosphoinositol 4,5-Bisphosphate J. Biol. Chem., January 16, 2009; 284(3): 1570 - 1582. [Abstract] [Full Text] [PDF]

				E. Polgar, K. M. Al-Khater, S. Shehab, M. Watanabe, and A. J. Todd Large Projection Neurons in Lamina I of the Rat Spinal Cord That Lack the Neurokinin 1 Receptor Are Densely Innervated by VGLUT2-Containing Axons and Possess GluR4-Containing AMPA Receptors J. Neurosci., December 3, 2008; 28(49): 13150 - 13160. [Abstract] [Full Text] [PDF]

				T. Sokabe, S. Tsujiuchi, T. Kadowaki, and M. Tominaga Drosophila Painless Is a Ca2+-Requiring Channel Activated by Noxious Heat J. Neurosci., October 1, 2008; 28(40): 9929 - 9938. [Abstract] [Full Text] [PDF]

				A. Dray Neuropathic pain: emerging treatments Br. J. Anaesth., July 1, 2008; 101(1): 48 - 58. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help