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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 19, 2007, 27(51):14147-14157; doi:10.1523/JNEUROSCI.4578-07.2007

This Article Full Text Full Text (PDF) Supplemental Data 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 (14) Citing Articles via Google Scholar Google Scholar Articles by Takashima, Y. Articles by McKemy, D. D. Search for Related Content PubMed PubMed Citation Articles by Takashima, Y. Articles by McKemy, D. D. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

 Previous Article  |  Next Article 

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

Yoshio Takashima,¹ Richard L. Daniels,¹ Wendy Knowlton,¹ James Teng,³ Emily R. Liman,^1,2 and David D. McKemy^1,2,3

¹Neuroscience Graduate Program, ²Neurobiology Section, Department of Biological Sciences, and ³School of Dentistry, University of Southern California, Los Angeles, California 90089

Correspondence should be addressed to Dr. David D. McKemy, 3641 Watt Way, HNB 228, University of Southern California, Los Angeles, CA 90089. Email: mckemy{at}usc.edu

Sensory nerves detect an extensive array of somatosensory stimuli, including environmental temperatures. Despite activating only a small cohort of sensory neurons, cold temperatures generate a variety of distinct sensations that range from pleasantly cool to painfully aching, prickling, and burning. Psychophysical and functional data show that cold responses are mediated by both C- and A-fibers with separate peripheral receptive zones, each of which likely provides one or more of these distinct cold sensations. With this diversity in the neural basis for cold, it is remarkable that the majority of cold responses in vivo are dependent on the cold and menthol receptor transient receptor potential melastatin 8 (TRPM8). TRPM8-null mice are deficient in temperature discrimination, detection of noxious cold temperatures, injury-evoked hypersensitivity to cold, and nocifensive responses to cooling compounds. To determine how TRPM8 plays such a critical yet diverse role in cold signaling, we generated mice expressing a genetically encoded axonal tracer in TRPM8 neurons. Based on tracer expression, we show that TRPM8 neurons bear the neurochemical hallmarks of both C- and A-fibers, and presumptive nociceptors and non-nociceptors. More strikingly, TRPM8 axons diffusely innervate the skin and oral cavity, terminating in peripheral zones that contain nerve endings mediating distinct perceptions of innocuous cool, noxious cold, and first- and second-cold pain. These results further demonstrate that the peripheral neural circuitry of cold sensing is cellularly and anatomically complex, yet suggests that cold fibers, caused by the diverse neuronal context of TRPM8 expression, use a single molecular sensor to convey a wide range of cold sensations.

Key words: TRPM8; cold temperatures; menthol; neural circuit; sensory neuron; transgenic

---

Received Aug. 16, 2007; revised Nov. 9, 2007; accepted Nov. 12, 2007.

Correspondence should be addressed to Dr. David D. McKemy, 3641 Watt Way, HNB 228, University of Southern California, Los Angeles, CA 90089. Email: mckemy{at}usc.edu

This article has been cited by other articles:

				M. Watanabe, Y. Sakuma, and M. Kato GABAA Receptors Mediate Excitation in Adult Rat GnRH Neurons Biol Reprod, August 1, 2009; 81(2): 327 - 332. [Abstract] [Full Text] [PDF]

				C. Morenilla-Palao, M. Pertusa, V. Meseguer, H. Cabedo, and F. Viana Lipid Raft Segregation Modulates TRPM8 Channel Activity J. Biol. Chem., April 3, 2009; 284(14): 9215 - 9224. [Abstract] [Full Text] [PDF]

				R. W. Carr, S. Pianova, D. D. McKemy, and J. A. Brock Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig cornea J. Physiol., March 15, 2009; 587(6): 1249 - 1264. [Abstract] [Full Text] [PDF]

				R. Madrid, E. de la Pena, T. Donovan-Rodriguez, C. Belmonte, and F. Viana Variable Threshold of Trigeminal Cold-Thermosensitive Neurons Is Determined by a Balance between TRPM8 and Kv1 Potassium Channels J. Neurosci., March 11, 2009; 29(10): 3120 - 3131. [Abstract] [Full Text] [PDF]

				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]

				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]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help