The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three-dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications.

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Diffusion tensor imaging: Concepts and applications

The abilities to sense environmental and internal temperatures are required for survival, both for maintenance of homeostasis and for avoidance of tissue-damaging noxious temperatures. Vertebrates can sense external physical stimuli via specialized classes of neurons in the peripheral nervous system that project to the skin. Temperaturesensitive neurons can be divided into two classes: innocuous thermosensors (warm or cool) and noxious thermonociceptors (hot or cold). ThermoTRPs, a subset of the transient receptor potential family of ion channels, which are expressed in sensory nerve endings and in skin, respond to distinct thermal thresholds. In this review, we examine the extent to which thermoTRPs are responsible for providing a molecular basis for thermal sensation.

https://www.cns.nyu.edu/~david/courses/sm12/Readings/Dhaka_etal%20AnnRevNeur2006.pdf

Trp ion channels and temperature sensation

Vertebrate cranial placodes I. Embryonic induction.

The multisensory perception of flavor.

One of the most intriguing features of taste perception is its modulation by temperature. It is well known that warming enhances perceived sweetness and bitterness. In addition, around half of the human population experiences taste sensations just by changing the temperature of the tongue, a phenomenon known as ‘thermal taste’. A possible molecular explanation for these thermal effects on taste is now at hand. Activation of the receptors for sweet, bitter and umami taste in specialized cells of the tongue causes opening of the TRPM5 ion channel. This channel has now been found to be activated by heat. Direct heat activation of TRPM5 could lead to activation of taste receptors even in the absence of anything to taste. TRPM5, a cation channel of the TRP superfamily, is highly expressed in taste buds of the tongue, where it has a key role in the perception of sweet, umami and bitter tastes1,2. Activation of TRPM5 occurs downstream of the activation of G-protein-coupled taste receptors and is proposed to generate a depolarizing potential in the taste receptor cells2. Factors that modulate TRPM5 activity are therefore expected to influence taste. Here we show that TRPM5 is a highly temperature-sensitive, heat-activated channel: inward TRPM5 currents increase steeply at temperatures between 15 and 35 °C. TRPM4, a close homologue of TRPM5, shows similar temperature sensitivity. Heat activation is due to a temperature-dependent shift of the activation curve, in analogy to other thermosensitive TRP channels3. Moreover, we show that increasing temperature between 15 and 35 °C markedly enhances the gustatory nerve response to sweet compounds in wild-type but not in Trpm5 knockout mice. The strong temperature sensitivity of TRPM5 may underlie known effects of temperature on perceived taste in humans4,5,6, including enhanced sweetness perception at high temperatures and ‘thermal taste’, the phenomenon whereby heating or cooling of the tongue evoke sensations of taste in the absence of tastants7.

/pdf/heat-activation-of-trpm5-underlies-thermal-sensitivity-of-1mdnc9d9zx.pdf

Heat activation of TRPM5 underlies thermal sensitivity of sweet taste

The first electrophysiological recordings from animal and human taste nerves gave clear evidence of thermal sensitivity, and studies have shown that as many as half of the neurons in mammalian taste pathways respond to temperature. Because temperature has never been shown to induce sensations of taste, it has been assumed that thermal stimulation in the gustatory system is somehow nulled. Here we show that heating or cooling small areas of the tongue can in fact cause sensations of taste: warming the anterior edge of the tongue (chorda tympani nerve) from a cold temperature can evoke sweetness, whereas cooling can evoke sourness and/or saltiness. Thermal taste also occurs on the rear of the tongue (glossopharyngeal nerve), but the relationship between temperature and taste is different there than on the front of the tongue. These observations indicate the human gustatory system contains several different types of thermally sensitive neurons that normally contribute to the sensory code for taste.

Thermal stimulation of taste

Although more acute in some areas of the body than in others, temperature sensitivity is assumed to be present throughout the skin. Only when very small stimuli have been used (e.g., approximately 1 mm2) has sensitivity to warming or cooling appeared discontinuous. Here we report the discovery of patches of skin several square centimeters in area within which heating cannot be detected until skin temperature exceeds the thresholds of C heat-sensitive nociceptors (>41 degrees C). These warmth-insensitive fields (> or = 5 cm2), which appear to lack low-threshold warm fibers, were also found to have reduced responsiveness to non-painful heating and significantly higher heat pain thresholds compared to surrounding areas of skin. The existence of such sites corroborates reports that warm fibers are rare in human cutaneous nerves and confirms the classical theory that cutaneous innervation by the warmth sense is punctate and sparse. The insensitive areas also provide unique opportunities for assessing the contribution of the low-threshold warmth system to perception of heat and heat pain, and their existence in healthy young adults contraindicates use of warmth sensitivity in neurological assessments of C-fiber function.

Alberto Cruz

Papers

Thermal stimulation of taste

"Warmth-insensitive fields": evidence of sparse and irregular innervation of human skin by the warmth sense