Have you ever wondered why after you brush your teeth with menthol toothpaste even tepid water seems really cool? Or how certain odors elicit powerful memories and responses? Two entertaining and highly informative presentations in the Neurobiology session had everyone nodding in recognition of these phenomena. Linda Buck (Fred Hutchinson Cancer Research Center, Seattle, USA) chaired the session and also gave a talk on odorant receptors (ORs) in the nasal epithelium (in October, Buck, together with Richard Axel, was awarded the Nobel Prize in Physiology or Medicine for her work on these receptors).
About a thousand different ORs are expressed in the olfactory sensory neurons. Each neuron expresses a single OR and the receptors are used repeatedly and combinatorially, such that each odor has a distinctive OR code. But with billions of possible codes, how do we discriminate odors? Buck described the use of a transgenic tracer to investigate the spatial input of nasal epithelial cells to the olfactory bulb and the cortex. Although neurons with the same OR are scattered around in the nose, they converge on specific locations in the olfactory bulb, on a few glomeruli. In turn, inputs from one OR are targeted to clusters of neurons at specific sites in the olfactory cortex, creating a stereotypic spatial map that is not related to that in the bulb. This means that single cortical neurons may receive combinatorial inputs from many different ORs, resulting in a stereotypic sensory map. Using c-Fos expression as an indicator of neuronal activation, Buck has found that different odorants elicit different but partially overlapping activation patterns in the cortex and that the representation of each odorant is composed of a small subset of sparsely distributed neurons.
Ardem Patapoutian (The Scripps Research Institute, La Jolla, USA) described the mechanisms of temperature sensation in relation to a family of genes encoding thermosensitive ion channels that have been uncovered in the past four years. These temperature-activated transient receptor potential (TRP) ion channels, or thermo-TRPs, are differentially expressed in a subset of dorsal root ganglia neurons and some are specialized to detect distinct temperature ranges - for example, there are cool channels and hot channels. In addition, they also respond to certain non-thermal agonists such as chemical compounds. In what Patapoutian described as a "drugstore experiment", he combed the drugstore shelves inspecting lists of ingredients of toothpaste, gum and mouthwash, looking for compounds that activate these ion channels. Compounds such as 'hot' cinnamon or capsaicin (the heat in hot chili peppers) and 'cool' menthol activate the channels and can be used to study temperature sensation mediated by the different thermo-TRPs. Previous work has identified some family members that respond to different temperatures and others that sense a noxious temperature, whether it is hot or cold. There are also thermo-TRPs that are activated within the innocuous temperature range of 34-42°C.
Patapoutian reported new studies on mice mutant for Trpv3, a warm-sensitive ion channel that is activated at 33°C. Because the commonly used hot-plate test does not cover this temperature range, Patapoutian devised a hot plate with a difference: one half was a warm 35°C and the other was cooler, at room temperature. Normal mice prefer the warmer temperature and spend more time on that side of the hot plate, whereas mutants for Trpv3 have no preference and spend equal time on either side, a nice demonstration that this ion-channel gene affects the sensing of warm temperature in vivo. It seems pretty obvious that temperature sensation within this range, as well as within the range of noxious temperatures, could have a selective advantage. Interestingly, Drosophila larvae have temperature preferences and will avoid a heated area; knockout of TrpA genes in Drosophila leads to loss of this avoidance behavior.
So why does menthol toothpaste make a drink of tepid water seem colder? The presence of menthol shifts the activation temperature of Trpm8 receptors to warmer temperatures, thus boosting the cooling effect and confounding the perception of absolute temperature. Like so much of the research at the conference, this rates as pretty cool.