The fear chemical?

June 29, 2011 § Leave a comment

We often talk, often rather vaguely, about instincts and how they shape our behavior (my instinctive reaction was…, etc.).  Predator-prey interactions are one place where instincts are real, and really matter. A cat that doesn’t realize that a little scuttling squeaky thing is also a good meal probably won’t be welcome in the barn of a corn farmer.  Similarly, if a mouse doesn’t know to avoid the lair of a fox without having to be trained in avoidance, that mouse is at severe risk of not getting a chance to pass on its genes to its progeny. Hard-wired responses to the smell of predators are well documented, but not well understood.  A new paper from a multi-disciplinary collaboration led by our close neighbor Stephen Liberles (and including our even closer neighbor Bob Datta) has identified one of the chemical components that lead to this response (Ferrero et al. 2011. Detection and avoidance of a carnivore odor by prey.  PNAS doi/10.1073/pnas.1103317108).

Ever since the pioneering work of Linda Buck and Richard Axel, we’ve known, roughly, where our experience of smell comes from: volatile odorants are detected by a large class of receptors expressed in the neurons of the olfactory epithelium.  Each neuron expresses just one receptor. A scent is typically a mixture of many odorants, each of which may bind to and trigger the activity of several receptors; the combination of neurons activated by a given scent is unique to that scent, and so each scent sends a distinct set of signals to our brains.  As a result of this combinatorial detection, we can discriminate an extremely wide range of scents with a relatively limited set of receptor molecules.  Stephen Liberles and Linda Buck later identified a second set of receptors that detect amine odorants, the “trace amine-associated receptors” or TAARs.  These receptors may detect some of the important signals mammals use to communicate with each other about, for example, their state of sexual receptiveness.  But in most cases the question of which odorant a specific receptor responds to has yet to be answered.  There’s no easy way to guess or deduce this: what you have to do is try various possible odorants and see which ones activate the receptors.  Luckily, since all odorant receptors respond to activation by causing an increase in the level of the second messenger cyclic AMP (cAMP), this is now possible to do in vitro: you express your receptor of interest in an ordinary cell line, making sure that the cell line has the appropriate machinery to connect the receptor to the adenyl cyclase that makes cAMP.  Then you add a cAMP-responsive reporter gene.  And then you try every possible odorant you can think of, and look for blips in reporter gene expression.  Then you move on to the next odorant receptor, and do it all again.

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