Happy hour: And how do we smell?

Some of my colleagues work on olfaction, and understanding how we manage to smell. So some of their work got me thinking about how this elementary sensory process occurs.

How do we manage to detect and discriminate between many, many, many different types of odors? How is it even important to us?

It’s something we rarely think about, and take for granted. But think about even modern life without smell. We don’t realize it, but the olfactory system, the system dealing with smell, controls many physiological processes, including regulating various hormones. Smell also has emotional responses (fear, happiness or repulsion) directly associated with it. And taste is highly dependent on smelling the food. In addition, smell also has reproductive functions, better understood in rodents or flies, but perhaps just as important in humans as well.

The process is clearly important, and was even recognized by a Nobel prize in 2004 (for Axel and Buck).

But how does this process occur?

We’ll just keep our understanding to mammals (yup, that includes us) and avoid the just as complex and fascinating system in insects or birds, or fish or amphibians (yes, fish can smell too. The famous Pacific Salmon swim thousands of miles away, but come back to the place the very were born in order to spawn, tracking their way back by smell).

In mammals olfaction starts in the nasal cavity, just beyond the nostrils. Here, a plethora of volatile molecules (the odorants) are detected by the olfactory epithelium. This structure is as fascinating as it is complex. It is enervated by thousands of nerve cells, called neurons. These neurons end in fine structures called cilia, lining the olfactory epithelium, where the odorant molecules can be picked up. Now, there are specific proteins called odorant receptors. These are large proteins found in these neurons, and these proteins can bind odorants. The fascinating theory (and theory in science does not mean an idea or hypothesis, but something that has a lot of scientific evidence to back it up. Gravity, relativity and evolution are theories) is that each one of these neurons has only one type of odorant receptor.

Here’s where it starts to get complex. There are thousands of neurons spread across the olfactory epithelium. Humans have about three hundred different odorant receptors (mice or dogs have even more). So, there are at least three hundred different types of neurons (with one type of odorant receptor each) in the epithelium. Each odorant receptor can bind not one, but many (specific) different odorants, but with different affinities. So, lets say the rose odorant molecule is bound by a set of ten different odorant receptors. The remaining 290 don’t bind it. But even these ten bind it with different affinities. So this creates a fine tuning that enables difference between many many times more than 300 odorants that can easily be detected.
What happens next is the key. These odorant receptors in these neurons bind an odorant. The neurons are long cells, going deep in to a brain region called the olfactory bulb. They end here in structures called glomeruli. Each type of neuron (with one odorant receptor) ends in a specific glomeruli.

But what happens when the odorant binds? How is the message actually transmitted?

Here’s what happens. When the odorant molecule binds that odorant receptor in the neuron, it triggers a few adjacent proteins, which go on to cause the synthesis and release of small molecules, called second messengers. These number in the thousands for every single odorant molecule that binds. So, there is a natural amplification. These molecules travel down the neuronal cell, and cause it to release a neurotransmitter (seen those ads on TV, for anti-depressant drugs, where a cartoon of one molecule releasing a thousand molecules happens? That stuff is real). These released neurotransmitters can now go across and bind their own specific receptor proteins, which will trigger an influx or efflux of positive or negatively charged ions (sodium, potassium, chlorine, calcium), through ion channels.

This creates a potential gradient, and this electric current is what’s transmitted to the brain for processing.

More modern techniques are now revealing that each odorant molecule actually “lights up” or works in different parts of the brain, by furiously triggering transcriptional events. This results in a chain of reactions, with specific proteins being made, activated, removed or inhibited. The brain then forms a specific memory for an odorant, registers it, and subsequently remembers it for future reference.

And that’s how we remember one smell from another.

What’s equally fascinating is that this olfactory epithelium is a region of constant churn. Most neurons don’t regenerate. If neurons in most of your brain die out, they wont come back (and this is what happens in Parkinson’s or Alzheimer’s disease, or just plain old age. Neurons die, don’t come back, and we lose brain function). Not in the olfactory system though. There are specific “neuronal stem cells” that constantly replace dying olfactory neurons. Normal neurons suffer constant abuse (some nasal inhalers are especially nasty in killing olfactory neurons), but many are replaced.

Replaced, 24 hours a day, seven days a week, until we die. But the battle is a struggle, and replacement often cannot keep up with destruction, so we suffer losses in our sense of smell.

But smell we do, and life’s that much better thanks to that!

Postscript: I purposely avoided the just as fascinating processes that pheromones participate it.