You can't trust your receptors: Smell

Food smells better when you're hungry, right? This is a common phenomenon that everyone I've ever talked to on the subject has experienced. For a long time, I assumed that the entire process underlying this phenomenon is in the brain proper, and not in the olfactory epithelium (that is, the smell receptors themselves).  However, a study on the adorable (and totally weird) salamander known as the 'Axolotl' suggests that the brain proper can actually modulate how sensitive those smell receptors are.

Axolotls (source)

yes, it does make a good pokemon character

Before I start explaining, let it be known that I am not saying the brain proper doesn't contribute to the 'food-smells-better-when-you're-hungry' phenomenon, in fact I would be very surprised if it didn't involve modulation of the ventral tegmental area, nucleus accumbens, and hypothalamus.

Mousley et al. (2006) use a technique called electro-olfactogram (EOG) to record the signals from smell receptors.  When the cells are excited by an odor, the size of the response can be recorded. They are using this technique in Axolotls, but it can be used in humans too:

EOG recording in humans (source)

Using this technique, Mousley et al. tested whether the size of the smell cells' signal could be modulated by a neuropeptide that is found in the terminal nerve (the nerve that connects the brain proper to the smell-sensing cells).  Chemicals that 'act like' this peptide can have confounding side effects, so the experimentors went to a lot of trouble to make sure they were using the peptide that is actually expressed in these animals.  They copied and synthesized this peptide from the genome of the axolotl. 

So what did they find? The found that this peptide (NPY) could modulate the size of the EOG response in hungry axolotls.  They applied the same amount of odor molecule and the same amount of NPY for each recording, so the increase in response is not due to more odor molecules or more NPY being present.  They suggest that it might be due to mory NPY receptors on the smell cells themselves, indicating that when hungry, the  smell cells change in these animals. 



Mousley et al., 2006 Fig4

So what does that mean? It means that when the animal is hungry, the brain proper has the ability to change the excitability of the smell receptors by dropping some NPY on them (through the terminal nerve).

This study showed the one specific peptide had an effect, but the principle that the brain can actually change the way the peripheral receptors sense things really struck me.  I had always thought that the receptors were pretty much stable, and pretty much always sent the same signal to the brain, but that the way the brain interpreted  that signal could be different. It fundamentally changed my view of sensory cells to learn that the smell receptors don't always send the same signals to the brain. 

source

  It made me rethink the studies that show expectation of taste changes the interpretation. The north dakota wine studies, and the wine-taste evaluation studies show that people rate things differently depending on what they are expecting. A common response is 'ha, what idiots to be influenced by the label of the wine and not trust their own tastebuds' when one reads about studies that show people evaluate white wines with red food coloring as if they were red wines and the like.

However, now I give these wine tasters more credit.  Perhaps the untrustworthy smell cells were actually altered by the brain's expectation. I haven't seen any study testing this idea with EOGs on humans, but I think it would make a great experiment.   

 
Mousley A, Polese G, Marks NJ, & Eisthen HL (2006). Terminal nerve-derived neuropeptide y modulates physiological responses in the olfactory epithelium of hungry axolotls (Ambystoma mexicanum). The Journal of neuroscience : the official journal of the Society for Neuroscience, 26 (29), 7707-17 PMID: 16855098