The Enigmatic Olfactory Tubercle: An Understudied Part of the Brain That May Hold the Key to the Powerful Nature of Smell
By Robin Latham
A whiff of chlorine can bring
memories of a lazy summer by
Why is it that a whiff of chlorine makes your best friend from grade school happy, remembering lazy summer days by the pool? But for you, it just reminds you of that heartbreaking summer when you were madly in love with a lifeguard.
It's well known that the same smell can be pleasant to one person, but unattractive to another. What makes an odor pleasing or offensive—what scientists call the hedonics of smell—is something that has puzzled researchers for decades. Yet no one has been able to locate where the association between smell and preference happens in the brain. But now, NIDCD researchers who study smell are beginning to take a fresh look at an understudied area of the brain that may play a key role in helping us decide why we turn our noses up at some smells and take another delightful sniff of others.
It might be hard to believe, but even today there are parts of the brain that aren't well explored. One such place is called the olfactory tubercle, an area located near the bottom of the front of the brain. The olfactory tubercle and the adjacent piriform cortex are major components of the olfactory system. They receive direct inputs from the olfactory bulb, which is connected to the specialized olfactory receptor neurons in the nose. Olfactory receptors are located in a small patch of tissue high inside the nose. They bind onto certain odor molecules and then transmit electrical signals to the olfactory bulb. The olfactory bulb sorts these signals and relays the message in the form of a smell-specific code to the olfactory tubercle and piriform cortex.
"It's a short, sweet system that allows for information to be extracted quickly," says Donald Wilson, Ph.D., an NIDCD-funded researcher at the New York University School of Medicine and the Nathan S. Kline Institute for Psychiatric Research in Orangeburg, N.Y. "In the olfactory system, you're only two synapses away from the important regions of the brain." In three steps, smell goes from an odor wafting outside the nose, to a signaled code, to a perception deep inside the brain. That means there aren't many places for olfactory code to be changed or attached to a certain preference.
Surprisingly, even though the olfactory tubercle was identified more than a century ago as being part of the olfactory system, it is much better known for the role it plays in the brain's reward system. The tubercle is part of a pathway deep in the center of the brain, which includes a number of other structures, including the amygdala and the hippocampus (known for their role in learning, emotion, and memory). This pathway regulates and controls behavior through the release of dopamine, a neurotransmitter or chemical messenger in several reward and motivational systems of the brain.
"More than a thousand papers have been written in the last ten years about the link between the olfactory tubercle and the brain's reward system," says Wilson. "But from an olfactory point of view, we really don't know what happens in there once the signal arrives from the olfactory bulb."
A substantial amount of research had been done to map the olfactory tubercle's anatomy and neurochemistry in regard to olfaction, but functional studies had lagged behind. Wilson and one of his post doctoral fellows, Daniel Wesson, Ph.D., decided to take a closer look. They were intrigued by the location of the olfactory tubercle at the nexus of the reward and olfactory systems and its potential for linking smell to preference. In spite of a lot of looking, no one had yet worked out where in the brain that link happened.
"If you look at the anatomy of the olfactory tubercle, it's in a prime position for performing this function," says Wesson. Information about smell streams into the piriform cortex and the olfactory tubercle, but only the tubercle is so intimately connected with the brain's reward system.
What's Sound Got to Do with It?
The team set out to investigate the olfactory tubercle using mouse models. They planned their experiments around basic olfactory questions, such as whether the cells could discriminate between odors, which was something that had yet to be answered. But soon after they began, Wesson accidentally made a loud "clink" setting down his coffee mug next to the lab apparatus, and discovered that the tubercle cells responded to the sound. Sound? Wasn't it supposed to be smell?
Before they further explored the effect of sound, the team had to verify that the cells also responded to smell. They did. More than 65 percent of the tubercle cells were activated by at least one of the five odors presented. Some cells responded to single odorants and some responded to two or three or more. This was what the researchers had been hoping for—to show that the tubercle could discriminate among odors.
Then it got more interesting. The two decided to see if sound had any influence on the level of response to odor. They introduced different mixes of odors and tones to the cells and found that the response in almost a third of them was either elevated or suppressed depending on whether the tone was present with the odor. Sound was raising or lowering the response of the cells to smell.
Just what role sound might play in the whole process is unclear, but for Wesson and Wilson, this discovery has opened the door more widely to a new way of thinking about the role of the tubercle in the olfactory system. If sound can change the perception of odor in the tubercle, could there be other things going on in the tubercle that might influence our preferences for certain smells? Wilson is optimistic. "It could be that the olfactory tubercle is a multipurpose area and the olfactory information streaming in only connects with neurons that have nothing to do with reward, but that seems unlikely," says Wilson.
What seems more likely, and which will hopefully be revealed with further experiments, is that the olfactory tubercle, with its strong, direct input from the olfactory bulb and its direct links to arousal, reward, and emotional circuits, may be the place where associations between smell and pleasure or aversion happen. It could very well explain why smell is so tied up with our emotions that just a wisp of an odor can flood our minds with sweet memories or remind us of our first bout of unrequited love.
Read about Dr. Wesson's research in The Journal of Neuroscience, or read the abstract in Pub Med.