Dr Ben Seymour, Computational and Biological Learning Lab, Trumpington Street, Cambridge CB2 1PZ


Center for Information and Neural Networks, National Institute for Information and Communications Technology (NICT), 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.

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Sensation is cool.

Humans have an amazing ability to sense temperature, with some people able to detect changes as little as 0.05C. How we do this is a bit of a mystery. Cold sensation is mediated in the periphery by the TRP family of thermoceptors, but there don’t seem to be enough known members of TRP family (each having an optimal temperature tuning response function) to code the full range of detectable temperatures with sufficient accuracy. Unless there is an as yet undiscovered large new family of thermoreceptors, then this suggests either:

  • 'Hyper-acuity' is achieved by sophisticated central brain decoding processes.
  • Each TRP receptor can adaptively and optimally tune itself to the ambient temperature, and so detect very small changes.

There's also a second, related, puzzle iwhen it comes to temperature: why is the perception of temperature strongly determined by relative temperature differences, such that a tepid bowl of water will feel cold to a hot hand, but warm to a cold hand? Again, this suggests eitehr central or peripheral processes:

  • There is a central topographic ‘state-thermometer’, sensitive to the ambient environmental temperature, against which phasic perturbations in temperature are judged.
  • Peripheral TRP thermoceptors do the adapting themselves.

Clearly both puzzles could be at least in part explained by peripheral adaptivity. In a recent study in the Journal of Neuroscience, Fujita and colleagues meaured cytosolic Ca2+ influx in cultured cells, and show that the TRPM8 cold receptor response is strongly determined by the ambient temperature of the cell before a phasic change in temperature. At 40C the temperature threshold was 35C, whereas at 30C the threshold was 28C, implying that the sensitivity to phasic temperature changes is increased in the region of ambient temperature. This is the case regardless of whether the cell arrives at this temperature from slow warming or slow cooling.  This implies temperature-sensitive molecular mechanisms that operate over different timescales, and that neuronal responses could be a function of the comparison between two underlying molecular processes. They go on to identify one such candidate mechanism, phosphatidylinositol 4,5-bisphosphate (PIP2) - which is known to be an important regulator of TRPM8 function. Intracellular depletion impairs the dependency on ambient temperature, and mutations to the binding site of PIP2 on the TRPM8 receptor also abolish the effect, providing good evidence for the necessity of PIP2 - TRPM8 signaling.

These results suggest that TRPM8 receptors ‘tune’ themselves to the ambient temperature, and hence are more sensitive to phasic changes. This illustrates a potential peripheral contribution to the adaptivity and hyper-acuity problems.

Many interesting questions emerge: what are the response properties from lower temperatures (such as 20C)? How does it interact with TRPM8 ligands such as menthol? To what extent these processes underlie behavioural and perceptual aspects of cold perception? Notwithstanding this, the results provide an important new finding in our understanding of thermosensory processing and perception.

Fujita F, Uchida K, Takaishi M, Sokabe T, Tominaga M. Ambient temperature affects the temperaature threshold for TRPM8 activation through interaction of phosphatatidylinositol 4,5- bisphosphate. J Neurosci. 2013 Apr 3; 33(14):6154-9

Based on a F1000 review with Hiro Mano 

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