Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Gold, Paul / Holsboer, Florian / Korth, Carsten / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John

8 Issues per year


IMPACT FACTOR 2016: 2.546
5-year IMPACT FACTOR: 3.191

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 0.980
Source Normalized Impact per Paper (SNIP) 2017: 0.804

Online
ISSN
2191-0200
See all formats and pricing
More options …
Volume 28, Issue 1

Issues

Highway to thermosensation: a traced review, from the proteins to the brain

Ivan Ezquerra-Romano
  • Corresponding author
  • Department of Cognitive, Perception and Brain Science, University College London, Gower Street, London WC1E 6BT, United Kingdom of Great Britain and Northern Ireland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Angel EzquerraORCID iD: http://orcid.org/0000-0002-5736-9867
Published Online: 2016-10-18 | DOI: https://doi.org/10.1515/revneuro-2016-0039

Abstract

Temperature maintenance and detection are essential for the survival and perpetuation of any species. This review is focused on thermosensation; thus a detailed and traced explanation of the anatomical and physiological characteristics of each component of this sensation is given. First, the proteins that react to temperature changes are identified; next, the nature of the neurons involved in thermosensation is described; and then, the pathways from the skin through the spinal cord to the brain are outlined. Finally, the areas of the brain and their interconnections where thermoperception arises are explained. Transduction of the external and internal temperature information is essentially mediated by the transient receptor potential ion channels (TRPs). These proteins are embedded in the neurons’ membrane and they hyper- or de-polarize neurons in function of the intrinsic voltage and the temperature changes. There are distinct TRP sensors for different temperature ranges. Interestingly, the primary afferent neurons have either cold or hot receptors, so they are dedicated separately to cold or hot sensation. The information is transmitted by different pathways from the skin to the brain, where it either remains separated or is integrated to generate a response. It seems that both the determination of how thermoperception is produced and how we interact with the world are dependent on the particular arrangement and nature of the components, the way of transduction of information and the communication between these elements.

Keywords: labelled-line principle; temperature; thermoperception; thermoreceptors; transient receptor potential ion channels (TRPs)

References

  • Adair, R.K. (1999). A model of the detection of warmth and cold by cutaneous sensors through effects on voltage-gated membrane channels. Proc. Nat. Acad. Sci. USA 96, 11825–11829.Google Scholar

  • Andrew, D. and Craig, A. (2001). Spinothalamic lamina I neurones selectively responsive to cutaneous warming in cats. J. Physiol. 537, 489–495.Google Scholar

  • Arrigoni, C., Rohaim, A., Shaya, D., Findeisen, F., Stein, R.A., Nurva, S.R.,... Minor, D.L. (2016). Unfolding of a temperature-sensitive domain controls voltage-gated channel activation. Cell 164, 922–936.Google Scholar

  • Askwith, C.C., Benson, C.J., Welsh, M.J., and Snyder, P.M. (2001). DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature. Proc. Nat. Acad. Sci. USA 98, 6459–6463.Google Scholar

  • Bagriantsev, S.N., Clark, K.A., and Minor, D.L., Jr. (2012). Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains. EMBO J. 31, 3297–3308.Google Scholar

  • Bautista, D.M., Siemens, J., Glazer, J.M., Tsuruda, P.R., Basbaum, A.I., Stucky, C.L.,... Julius, D. (2007). The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448, 204–208.Google Scholar

  • Bear, M.F., Connors, B.W., and Paradiso, M.A. (2007). Neuroscienze. esplorando il cervello. With CD-ROM Elsevier srl.Google Scholar

  • Benham, C.D., Gunthorpe, M.J., and Davis, J.B. (2003). TRPV channels as temperature sensors. Cell Calcium 33, 479–487.Google Scholar

  • Boulant, J. (1980). Hypothalamic control of thermoregulation: neurophysiological basis. Handbook of the Hypothalamus 3, 1–82.Google Scholar

  • Boulant, J. (1998). Hypothalamic neurons: mechanisms of sensitivity to temperature. Ann. NY Acad. Sci. 856, 108–115.Google Scholar

  • Boulant, J.A. (2000). Role of the preoptic-anterior hypothalamus in thermoregulation and fever. Clin. Infect. Dis. 31, S157–S161.Google Scholar

  • Boulant, J.A. and Dean, J.B. (1986). Temperature receptors in the central nervous system. Annu. Rev. Physiol. 48, 639–654.Google Scholar

  • Boulant, J.A. and Gonzalez, R.R. (1977). The effect of skin temperature on the hypothalamic control of heat loss and heat production. Brain Res. 120, 367–372.Google Scholar

  • Boulant, J.A. and Hardy, J.D. (1974). The effect of spinal and skin temperatures on the firing rate and thermosensitivity of preoptic neurones. J. Physiol. 240, 639–660.Google Scholar

  • Brauchi, S., Orio, P., and Latorre, R. (2004). Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc. Nat. Acad. Sci. USA 101, 15494–15499.Google Scholar

  • Brauchi, S., Orta, G., Salazar, M., Rosenmann, E. and Latorre, R. (2006). A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels. J. Neurosci. 26, 4835–4840.Google Scholar

  • Brooks, J.C., Nurmikko, T.J., Bimson, W.E., Singh, K.D., and Roberts, N. (2002). fMRI of thermal pain: effects of stimulus laterality and attention. NeuroImage 15, 293–301.Google Scholar

  • Campbell, J.N. and LaMotte, R.H. (1983). Latency to detection of first pain. Brain Res. 266, 203–208.Google Scholar

  • Carpenter, D.O. (1967). Temperature effects on pacemaker generation, membrane potential, and critical firing threshold in aplysia neurons. J. Gen. Physiol. 50, 1469–1484.Google Scholar

  • Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D., and Julius, D. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816–824.Google Scholar

  • Caterina, M.J., Rosen, T.A., Tominaga, M., Brake, A.J., and Julius, D. (1999). A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398, 436–441.Google Scholar

  • Chen, X., Hosono, T., Yoda, T., Fukuda, Y., and Kanosue, K. (1998). Efferent projection from the preoptic area for the control of non-shivering thermogenesis in rats. J. Physiol. 512, 883–892.Google Scholar

  • Chowdhury, S., Jarecki, B.W., and Chanda, B. (2014). A molecular framework for temperature-dependent gating of ion channels. Cell 158, 1148–1158.Google Scholar

  • Chung, M.K., Guler, A.D., and Caterina, M.J. (2005). Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3. J. Biol. Chem. 280, 15928–15941.Google Scholar

  • Clapham, D.E. (2003). TRP channels as cellular sensors. Nature 426, 517–524.Google Scholar

  • Clapham, D.E. and Miller, C. (2011). A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels. Proc. Nat. Acad. Sci. USA 108, 19492–19497.Google Scholar

  • Clapham, D.E., Runnels, L.W., and Strübing, C. (2001). The TRP ion channel family. Nat. Rev. Neurosci. 2, 387–396.Google Scholar

  • Cosens, D., and Manning, A. (1969). Abnormal electroretinogram from a Drosophila mutant. Nature 224, 285–287.Google Scholar

  • Craig, A.D. (2002). How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 3, 655–666.Google Scholar

  • Craig, A. (2003). A new view of pain as a homeostatic emotion. Trends Neurosci. 26, 303–307.Google Scholar

  • Craig, A.D. and Bushnell, M.C. (1994). The thermal grill illusion: unmasking the burn of cold pain. Science 265, 252–255.Google Scholar

  • Craig, A.D. and Dostrovsky, J.O. (2001). Differential projections of thermoreceptive and nociceptive lamina I trigeminothalamic and spinothalamic neurons in the cat. J. Neurophysiol. 86, 856–870.Google Scholar

  • Craig, A., Reiman, E., Evans, A., and Bushnell, M. (1996). Functional imaging of an illusion of pain. Nature 384, 258–260.Google Scholar

  • Craig, A.D., Chen, K., Bandy, D., and Reiman, E.M. (2000). Thermosensory activation of insular cortex. Nat. Neurosci. 3, 184–190.Google Scholar

  • Davis, K.D. and Pope, G.E. (2002). Noxious cold evokes multiple sensations with distinct time courses. Pain 98, 179–185.Google Scholar

  • Davis, K.D., Lozano, R.M., Manduch, M., Tasker, R.R., Kiss, Z.H., and Dostrovsky, J.O. (1999). Thalamic relay site for cold perception in humans. J. Neurophysiol. 81, 1970–1973.Google Scholar

  • Davis, J.B., Gray, J., Gunthorpe, M.J., Hatcher, J.P., Davey, P.T., Overend, P., Harries MH, Latcham J, Clapham C, Atkinson, K., et al. (2000). Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405, 183–187.Google Scholar

  • del Camino, D., Murphy, S., Heiry, M., Barrett, L.B., Earley, T.J., Cook, C.A., Petrus, MJ., Zhao, M., D’Amours, M., Deering, N., et al. (2010). TRPA1 contributes to cold hypersensitivity. J. Neurosci. 30, 15165–15174.Google Scholar

  • Dhaka, A., Earley, T.J., Watson, J., and Patapoutian, A. (2008). Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J. Neurosci. 28, 566–575.Google Scholar

  • Frank, D.D., Jouandet, G.C., Kearney, P.J., Macpherson, L.J., and Gallio, M. (2015). Temperature representation in the drosophila brain. Nature 519, 358–361.Google Scholar

  • Gallio, M., Ofstad, T.A., Macpherson, L.J., Wang, J.W., and Zuker, C.S. (2011). The coding of temperature in the drosophila brain. Cell 144, 614–624.Google Scholar

  • Grandl, J., Hu, H., Bandell, M., Bursulaya, B., Schmidt, M., Petrus, M., and Patapoutian, A. (2008). Pore region of TRPV3 ion channel is specifically required for heat activation. Nat. Neurosci. 11, 1007–1013.Google Scholar

  • Guler, A.D., Lee, H., Iida, T., Shimizu, I., Tominaga, M., and Caterina, M. (2002). Heat-evoked activation of the ion channel, TRPV4. J. Neurosci. 22, 6408–6414.Google Scholar

  • Halvorson, I. and Thornhill, J. (1993). Posterior hypothalamic stimulation of anesthetized normothermic and hypothermic rats evokes shivering thermogenesis. Brain Res. 610, 208–215.Google Scholar

  • Han, Z., Zhang, E., and Craig, A. (1998). Nociceptive and thermoreceptive lamina I neurons are anatomically distinct. Nat. Neurosci. 1, 218–225.Google Scholar

  • Hardie, R.C., Martin, F., Cochrane, G., Juusola, M., Georgiev, P., and Raghu, P. (2002). Molecular basis of amplification in drosophila phototransduction: roles for G protein, phospholipase C, and diacylglycerol kinase. Neuron 36, 689–701.Google Scholar

  • Hensel, H. and Zotterman, Y. (1951). The response of the cold receptors to constant cooling. Acta Physiol. Scand. 22, 96–105.Google Scholar

  • Hille, B. (2001). Ion Channels of Excitable Membranes (Sunderland, MA: Sinauer).Google Scholar

  • Holstege, G. (1988). Direct and indirect pathways to lamina I in the medulla oblongata and spinal cord of the cat. Progr. Brain Res. 77, 47–94.Google Scholar

  • Hori, A., Minato, K., and Kobayashi, S. (1999). Warming-activated channels of warm-sensitive neurons in rat hypothalamic slices. Neurosci. Lett. 275, 93–96.Google Scholar

  • Irie, K., Shimomura, T., and Fujiyoshi, Y. (2012). The C-terminal helical bundle of the tetrameric prokaryotic sodium channel accelerates the inactivation rate. Nat. Commun. 3, 793.Google Scholar

  • Jiang, Y., Lee, A., Chen, J., Cadene, M., Chait, B.T., and MacKinnon, R. (2002). Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417, 515–522.Google Scholar

  • Kenshalo, D.R., Holmes, C.E., and Wood, P.B. (1968). Warm and cool thresholds as a function of rate of stimulus temperature change. Percept. Psychophys. 3, 81–84.Google Scholar

  • LaMotte, R.H. and Campbell, J.N. (1978). Comparison of responses of warm and nociceptive C-fiber afferents in monkey with human judgments of thermal pain. J. Neurophysiol. 41, 509–528.Google Scholar

  • Lee, H.M., Cho, C.K., Yun, M.H., and Lee, M.W. (1998). Development of a temperature control procedure for a room air-conditioner using the concept of just noticeable difference (JND) in thermal sensation. Int. J. Ind. Ergonom. 22, 207–216.Google Scholar

  • Lenz, F.A., Seike, M., Richardson, R.T., Lin, Y.C., Baker, F.H., Khoja, I., Jaeger, C.J., Gracely, R.H. (1993). Thermal and pain sensations evoked by microstimulation in the area of human ventrocaudal nucleus. J. Neurophysiol. 70, 200–212.Google Scholar

  • Lv, Y. and Liu, J. (2007). Effect of transient temperature on thermoreceptor response and thermal sensation. Build. Environ. 42, 656–664.Google Scholar

  • Mackenzie, R.A., Burke, D., Skuse, N.F., and Lethlean, A.K. (1975). Fibre function and perception during cutaneous nerve block. J. Neurol. Neurosurg. 38, 865–873.Google Scholar

  • Maingret, F., Lauritzen, I., Patel, A.J., Heurteaux, C., Reyes, R., Lesage, F., Lazdunski, M., Honore, E. (2000). TREK-1 is a heat-activated background K+ channel. EMBO J. 19, 2483–2491.Google Scholar

  • McKemy, D.D., Neuhausser, W.M., and Julius, D. (2002). Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416, 52–58.Google Scholar

  • Mezey, É, Tóth, Z.E., Cortright, D.N., Arzubi, M.K., Krause, J.E., Elde, R., Guo, A., Blumberg, P.M., Szallasi, A. (2000). Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc. Natl. Acad. Sci. USA 97, 3655–3660.Google Scholar

  • Minke, B. and Cook, B. (2002). TRP channel proteins and signal transduction. Physiol. Rev. 82, 429–472.Google Scholar

  • Mio, K., Mio, M., Arisaka, F., Sato, M., and Sato, C. (2010). The C-terminal coiled-coil of the bacterial voltage-gated sodium channel NaChBac is not essential for tetramer formation, but stabilizes subunit-to-subunit interactions. Prog. Biophys. Mol. Biol. 103, 111–121.Google Scholar

  • Montell, C., Birnbaumer, L., and Flockerzi, V. (2002). The TRP channels, a remarkably functional family. Cell 108, 595–598.Google Scholar

  • Mower, G.D. (1976). Perceived intensity of peripheral thermal stimuli is independent of internal body temperature. J. Comp. Physiol. 90, 1152.Google Scholar

  • Nagashima, K., Nakai, S., Tanaka, M., and Kanosue, K. (2000). Neuronal circuitries involved in thermoregulation. Auton. Neurosci. 85, 18–25.Google Scholar

  • Nagy, I. and Rang, H. (1999). Noxious heat activates all capsaicin-sensitive and also a sub-population of capsaicin-insensitive dorsal root ganglion neurons. Neuroscience 88, 995–997.Google Scholar

  • Nilius, B., Talavera, K., Owsianik, G., Prenen, J., Droogmans, G., and Voets, T. (2005). Gating of TRP channels: a voltage connection? J. Physiol. 567, 35–44.Google Scholar

  • Patapoutian, A., Peier, A.M., Story, G.M., and Viswanath, V. (2003). ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat. Rev. Neurosci. 4, 529–539.Google Scholar

  • Payandeh, J. and Minor, D.L. (2015). Bacterial voltage-gated sodium channels (BacNaVs) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart. J. Mol. Biol. 427, 3–30.Google Scholar

  • Pedersen, S.F., Owsianik, G., and Nilius, B. (2005). TRP channels: an overview. Cell Calcium 38, 233–252.Google Scholar

  • Peier, A.M., Reeve, A.J., Andersson, D.A., Moqrich, A., Earley, T.J., Hergarden, A.C., Story, G.M., Colley, S., Hogenesch, J.B., McIntyre, P., et al. (2002). A heat-sensitive TRP channel expressed in keratinocytes. Science 296, 2046–2049.Google Scholar

  • Pierau, F., Torrey, P., and Carpenter, D.O. (1974). Mammalian cold receptor afferents: role of an electrogenic sodium pump in sensory transduction. Brain Res. 73, 156–160.Google Scholar

  • Pioletti, M., Findeisen, F., Hura, G.L., and Minor, D.L. (2006). Three-dimensional structure of the KChIP1–Kv4. 3 T1 complex reveals a cross-shaped octamer. Nat. Struct. Mol. Biol. 13, 987–995.Google Scholar

  • Powl, A.M., O’Reilly, A.O., Miles, A.J., and Wallace, B.A. (2010). Synchrotron radiation circular dichroism spectroscopy-defined structure of the C-terminal domain of NaChBac and its role in channel assembly. Proc. Nat. Acad. Sci. USA 107, 14064–14069.Google Scholar

  • Price, D.D., Hu, J.W., Dubner, R., and Gracely, R.H. (1977). Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain 3, 57–68.Google Scholar

  • Price, D.D., Hayes, R.L., Ruda, M., and Dubner, R. (1978). Spatial and temporal transformations of input to spinothalamic tract neurons and their relation to somatic sensations. J. Neurophysiol. 41, 933–947.Google Scholar

  • Rhee, S.G., and Bae, Y.S. (1997). Regulation of phosphoinositide-specific phospholipase C isozymes. J. Biol. Chem. 272, 15045–15048.Google Scholar

  • Satinoff, E. (1978). Neural organization and evolution of thermal regulation in mammals. Science 201, 16–22.Google Scholar

  • Schepers, R.J. and Ringkamp, M. (2010). Thermoreceptors and thermosensitive afferents. Neurosci. Biobehav. Rev. 34, 177–184.Google Scholar

  • Shaya, D., Findeisen, F., Abderemane-Ali, F., Arrigoni, C., Wong, S., Nurva, S.R., Loussouarn, G., Minor, D.L. (2014). Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels. J. Mol. Biol. 426, 467–483.Google Scholar

  • Smith, G., Gunthorpe, M., Kelsell, R., Hayes, P., Reilly, P., Facer, P., Wright, J.E., Jerman, J.C., Walhin, J.P., Ooi, L. (2002). TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418, 186–190.Google Scholar

  • Souslova, V., Cesare, P., Ding, Y., Akopian, A.N., Stanfa, L., Suzuki, R., Carpenter, K., Dickenson, A., Boyce, S., Hill, R., et al. (2000). Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X 3 receptors. Nature 407, 1015–1017.Google Scholar

  • Story, G.M., Peier, A.M., Reeve, A.J., Eid, S.R., Mosbacher, J., Hricik, T.R., McIntyre, P., Jegla, T., Bevan, S., Patapoutian, A., et al. (2003). ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112, 819–829.Google Scholar

  • Stuart, D., Kawamura, Y., and Hemingway, A. (1961). Activation and suppression of shivering during septal and hypothalamic stimulation. Exp. Neurol. 4, 485–506.Google Scholar

  • Tillman, D., Treede, R., Meyer, R.A., and Campbell, J.N. (1995). Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold. J. Physiol. 485, 753–765.Google Scholar

  • Torvi, D. and Dale, J. (1994). A finite element model of skin subjected to a flash fire. J. Biomech. Eng 116, 250–255.Google Scholar

  • Treede, R., Meyer, R., Raja, S., and Campbell, J. (1995). Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin. J. Physiol. 483, 747–758.Google Scholar

  • Voets, T., Droogmans, G., Wissenbach, U., Janssens, A., Flockerzi, V., and Nilius, B. (2004). The principle of temperature-dependent gating in cold-and heat-sensitive TRP channels. Nature 430, 748–754.Google Scholar

  • Voets, T., Talavera, K., Owsianik, G., and Nilius, B. (2005). Sensing with TRP channels. Nat. Chem. Biol. 1, 85–92.Google Scholar

  • Vriens, J., Nilius, B., and Voets, T. (2014). Peripheral thermosensation in mammals. Nat. Rev. Neurosci. 15, 573–589.Google Scholar

  • Watanabe, H., Vriens, J., Suh, S. H., Benham, C.D., Droogmans, G., and Nilius, B. (2002). Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J. Biol. Chem. 277, 47044–47051.Google Scholar

  • Xu, H., Ramsey, I.S., Kotecha, S.A., Moran, M.M., Chong, J.A., Lawson, D., Ge, P., Lilly, J., Silos-Santiago, I., Xie, Y., et al. (2002). TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418, 181–186.Google Scholar

  • Yarnitsky, D. and Ochoa, J.L. (1990). Release of cold-induced burning pain by block of cold-specific afferent input. Brain 113, 893–902.Google Scholar

  • Yu, F.H., Yarov-Yarovoy, V., Gutman, G.A., and Catterall, W.A. (2005). Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacol. Rev. 57, 387–395.Google Scholar

  • Yuan, P., Leonetti, M.D., Pico, A.R., Hsiung, Y., and MacKinnon, R. (2010). Structure of the human BK channel Ca2+-activation apparatus at 3.0 Å resolution. Science 329, 182–186.Google Scholar

  • Zagotta, W.N., Olivier, N.B., Black, K.D., Young, E.C., Olson, R., and Gouaux, E. (2003). Structural basis for modulation and agonist specificity of HCN pacemaker channels. Nature 425, 200–205.Google Scholar

  • Zhang, Y., Yanase-Fujiwara, M., Hosono, T., and Kanosue, K. (1995). Warm and cold signals from the preoptic area: which contribute more to the control of shivering in rats? J. Physiol. 485, 195–202.Google Scholar

  • Zhang, E., Han, Z., and Craig, A. (1996). Morphological classes of spinothalamic lamina I neurons in the cat. J. Comp. Neurol. 367, 537–549.Google Scholar

  • Zhang, Y., Hoon, M.A., Chandrashekar, J., Mueller, K.L., Cook, B., Wu, D., Zuker, C.S., Ryba, N.J. (2003). Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112, 293–301.Google Scholar

About the article

Ivan Ezquerra-Romano

Ivan Ezquerra-Romano is an MSc Neuroscience undergraduate at University College London. His scientific interest is in consciousness, perception and neuropharmacology. He was awarded in the summer of 2016 with the Wellcome Trust Vacation Scholarship for doing research at his university in decision-making. He is also co-founder of a drugs harm reduction website (Drugsand.me) that provides reliable and evidence-based information for drug users.

Angel Ezquerra

Angel Ezquerra is a professor of Science Education in the Department of Didactics of Experimental Sciences, Complutense University of Madrid, Spain. His research is focused on the study of the inception of misconceptions in the understanding of physics. He has also carried out research on pedagogical content knowledge in science and on the strategies of teacher education.


Received: 2016-06-30

Accepted: 2016-08-07

Published Online: 2016-10-18

Published in Print: 2017-01-01


Citation Information: Reviews in the Neurosciences, Volume 28, Issue 1, Pages 45–57, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2016-0039.

Export Citation

©2017 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in