Why do some smells trigger emotional responses? (Kmpzzz/Shutterstock)

In a nutshell Researchers identified two distinct brain pathways that determine whether an odor feels pleasant or threatening, shedding light on how our brains emotionally interpret smells.

These same pathways influence fear-related behaviors in mice, including avoidance and fear learning, depending on where in the brain the signals are sent.

The findings may help explain why certain smells can trigger intense reactions in people with PTSD, anxiety, or sensory sensitivities, and open the door to more targeted treatments.

GAINESVILLE, Fla. — Your brain makes life-or-death decisions in milliseconds, and scientists just figured out exactly how it chooses between fight, flight, or freeze. New research reveals that two competing neural highways determine whether you’ll face danger head-on or hide under the covers. Understanding this wiring could finally explain why anxiety affects everyone differently.

Scientists at the University of Florida have also figured out how our brains decide whether a smell is pleasant or revolting. The same neural pathways that control fear also determine whether you love the aroma of fresh coffee or can’t stand the lingering scent of microwaved fish.

“Odors are powerful at driving emotions, and it’s long been thought that the sense of smell is just as powerful, if not more powerful, at driving an emotional response as a picture, a song or any other sensory stimulus,” says senior author Dan Wesson from the UF College of Medicine, in a statement.

The Brain’s Fear and Smell Network

The same areas in your brain that control fear determine if you like a smell or not. (Photo by Taylor Deas-Melesh from Unsplash)

The research, published in Molecular Psychiatry, focused on a brain region called the basolateral amygdala. This is the brain’s alarm system that decides whether something is dangerous or pleasant. This area connects to the ventral striatum, a region involved in motivation and movement.

“This is, in part, what we mean when we say your sense of smell is your most emotional sense,” says first author Sarah Sniffen from the UF College of Medicine. “Yes, smells evoke strong, emotional memories, but the brain’s smell centers are more closely connected with emotional centers like the amygdala.”

Using genetically modified mice, the researchers identified two distinct types of brain cells based on the genes they express, Drd1+ and Drd2+ neurons. They each carry specific information to different destinations.

Scientists tracked exactly where these neural pathways go and what happens when they’re activated or shut down. They injected special viruses that made specific brain cells glow under certain lights, allowing them to trace the complete circuit maps.

The study revealed that these two types of brain cells create parallel highways that lead to different neighborhoods in the ventral striatum. The first pathway (Drd1+ neurons) primarily connects to an area called the nucleus accumbens, while the second (Drd2+ neurons) mainly links to a region called the tubular striatum.

Initially, the team expected that one cell type would generate positive emotions while another would generate negative emotions. Instead, they discovered something more complex and potentially more powerful for future treatments.

“It can make an odor positive or negative to you,” says Wesson. “And it all depends upon where that cell type projects in your brain and how it engages with structures in your brain.”

When researchers artificially activated these pathways, they discovered the circuits had specific effects on behavior. Mice avoided areas where the Drd1+ pathway to the nucleus accumbens was stimulated, as well as areas where the Drd2+ pathway to the tubular striatum was activated, but in different ways.

Fear Learning and Smell Associations

The researchers then tested how these pathways affect learning to associate smells with danger, similar to how you might learn to fear the smell of smoke after experiencing a fire.

Monitoring the animals’ breathing patterns and movement, the team paired neutral odors with mild foot shocks. They then chemically silenced specific pathways during this learning process to see which circuits were necessary for forming fear memories.

Blocking the Drd1+ pathway to the nucleus accumbens significantly reduced fear learning, as did blocking the Drd2+ pathway to the tubular striatum. However, the other pathway combinations didn’t affect learning, showing that the destination matters as much as the origin.

Human Anxiety and Sensory Issues

This research was conducted in mice, but the brain structures involved are similar in humans.

“We’re constantly breathing in and out, and that means that we’re constantly receiving olfactory input,” says Sniffen. “For some people, that’s fine, and it doesn’t impact their day-to-day life. They might even think, ‘Oh, odors don’t matter that much.’ But for people who have a heightened response to sensory stimuli, like those with PTSD or anxiety or autism, it’s a really important factor for their day-to-day life.”

Smells can elicit strong emotions like anxiety or disgust. (Krakenimages.com/Shutterstock)

Modern anxiety medications largely work by broadly dampening brain activity throughout the brain. But this research suggests a more surgical approach might be possible, targeting specific pathways based on an individual’s particular symptom pattern.

This research could help clinicians address specific problems, like helping a patient who associates a clinic’s smell with transfusions that made them queasy, or restoring appetite in people who’ve grown indifferent to food due to illness.

Medications could potentially suppress some pathways’ activity to help people overcome stressful responses, or activate them to restore enjoyment to things people have lost interest in.

“Emotions in part dictate our quality of life, and we’re learning more about how they arise in our brain,” says Wesson. “Understanding more about how our surroundings can impact our feelings can help us become happier, healthier humans.”

Rather than treating all anxiety as the same disorder, we now have evidence that different fear responses run on different tracks. That means we can potentially start building treatments that actually match the problem.

You wouldn’t microwave fish around your worst enemy — the smell lingers both in kitchen and memory. It is one few of us like, let alone have positive associations with.

But what makes our brains decide a smell is stinky?

A new study from UF Health researchers reveals the mechanisms behind how your brain decides you dislike — even loathe — a smell.

Or as first author and graduate research fellow Sarah Sniffen puts it: How do odors come to acquire some sort of emotional charge?

In many ways, our world capitalizes upon the importance of smells to influence emotions, running the gamut from perfumes to cooking and even grocery store design.

“Odors are powerful at driving emotions, and it’s long been thought that the sense of smell is just as powerful, if not more powerful, at driving an emotional response as a picture, a song or any other sensory stimulus,” said senior author Dan Wesson, Ph.D., a professor of pharmacology and therapeutics in the UF College of Medicine and interim director of the Florida Chemical Senses Institute.

Read more …

Summary: A new study reveals how the brain determines whether a smell is pleasant or revolting, highlighting why scent evokes such strong emotional responses. Researchers focused on the amygdala, the brain’s emotional hub, and found two genetically distinct cell types that can make any odor feel good or bad, depending on where they project in the brain.

Contrary to expectations, these cells aren’t hardwired to one emotion—they’re flexible, able to assign either positive or negative value. This discovery could lead to treatments that help people with anxiety, PTSD, or sensory disorders reframe distressing smell-related experiences.

Key Facts:

Emotional Wiring: The olfactory system connects directly to the amygdala, amplifying emotional responses to smell.

The olfactory system connects directly to the amygdala, amplifying emotional responses to smell. Flexible Coding: Specialized brain cells can assign either positive or negative emotions to smells, depending on brain circuitry.

Specialized brain cells can assign either positive or negative emotions to smells, depending on brain circuitry. Clinical Potential: Findings could inform therapies for conditions like PTSD, where smell triggers harmful emotional memories.

Source: University of Florida

You wouldn’t microwave fish around your worst enemy — the smell lingers both in kitchen and memory. It is one few of us like, let alone have positive associations with.

But what makes our brains decide a smell is stinky?

A new study from UF Health researchers reveals the mechanisms behind how your brain decides you dislike — even loathe — a smell.

Based upon the receptor systems in these specific brain pathways, the team members believe they might be able to change those associations. Credit: Neuroscience News

Or as first author and graduate research fellow Sarah Sniffen puts it: How do odors come to acquire some sort of emotional charge?

In many ways, our world capitalizes upon the importance of smells to influence emotions, running the gamut from perfumes to cooking and even grocery store design.

“Odors are powerful at driving emotions, and it’s long been thought that the sense of smell is just as powerful, if not more powerful, at driving an emotional response as a picture, a song or any other sensory stimulus,” said senior author Dan Wesson, Ph.D., a professor of pharmacology and therapeutics in the UF College of Medicine and interim director of the Florida Chemical Senses Institute.

But until now, researchers have puzzled over what circuitry connects the parts of the brain vital to generating an emotional response with those responsible for smell perception.

The team started off with the amygdala, a brain region that curates your emotional responses to sensory stimuli. Although all our senses (sound, sight, taste, touch and smell) interact with this small part of your brain, the olfactory system takes a more direct route to it.

“This is, in part, what we mean when we say your sense of smell is your most emotional sense,” Sniffen said. “Yes, smells evoke strong, emotional memories, but the brain’s smell centers are more closely connected with emotional centers like the amygdala.”

In the study, researchers looked at mice, who share neurochemical similarities with people. They can learn about odors and categorize them as good or bad.

After observing their behavior and analyzing brain activity, the team found two genetically unique brain cell types that allow odors to be assigned into a bucket of good feelings or bad feelings.

Initially, the team expected that one cell type would generate a positive emotion to an odor, and another would generate a negative emotion. Instead, the brain’s cellular organization gives the cells the capability of doing either.

“It can make an odor positive or negative to you,” Wesson said. “And it all depends upon where that cell type projects in your brain and how it engages with structures in your brain.”

But why is knowing more about how we categorize smells important? Well, for starters, smells — and our reactions to them — are a part of life. Sometimes, however, our reactions to them can be outsized, or take on a negative association so strong it disrupts how we live.

“We’re constantly breathing in and out and that means that we’re constantly receiving olfactory input,” Sniffen said.

“For some people that’s fine, and it doesn’t impact their day-to-day life. They might even think, ‘Oh, odors don’t matter that much.’ But for people who have a heightened response to sensory stimuli, like those with PTSD or anxiety or autism, it’s a really important factor for their day-to-day life.”

In the future, the research could help clinicians adjust for heightened sensory response that some people struggle with in their everyday lives, Wesson added. One example? A patient associating a clinic’s smell with transfusions that made them queasy.

Based upon the receptor systems in these specific brain pathways, the team members believe they might be able to change those associations.

Potentially, medications could suppress some of these pathways’ activity to allow you to overcome stressful and aversive emotional responses.

Conversely, these pathways could be activated to restore enjoyment to things that people might have grown indifferent to — like those who lose their appetite from illness.

“Emotions in part dictate our quality of life, and we’re learning more about how they arise in our brain,” Wesson said. “Understanding more about how our surroundings can impact our feelings can help us become happier, healthier humans.”

About this olfaction research news

Author: Eric Hamilton

Source: University of Florida

Contact: Eric Hamilton – University of Florida

Image: The image is credited to Neuroscience News

Original Research: Open access.

“Directing negative emotional states through parallel genetically-distinct basolateral amygdala pathways to ventral striatum subregions” by Sarah Sniffen et al. Molecular Psychiatry

Abstract

Directing negative emotional states through parallel genetically-distinct basolateral amygdala pathways to ventral striatum subregions

Distinct basolateral amygdala (BLA) cell populations influence emotions in manners thought important for anxiety and anxiety disorders.

The BLA contains numerous cell types which can broadcast information into structures that may elicit changes in emotional states and behaviors.

BLA excitatory neurons can be divided into two main classes, one of which expresses Ppp1r1b (encoding protein phosphatase 1 regulatory inhibitor subunit 1B) which is downstream of the genes encoding the D1 and D2 dopamine receptors (Drd1 and Drd2 respectively).

The role of Drd1+ or Drd2+ BLA neurons in learned and unlearned emotional responses is unknown.

Here, we identified that the Drd1+ and Drd2+ BLA neuron populations form two parallel pathways for communication with the ventral striatum.

These neurons arise from the basal nucleus of the BLA, innervate the entire space of the ventral striatum, and are capable of exciting ventral striatum neurons.

Further, through two separate behavioral assays, we found that the Drd1+ and Drd2+ parallel pathways distinctly influence both learned and unlearned emotional states when they are activated or suppressed and do so depending upon where they synapse in the ventral striatum – with unique contributions of Drd1+ and Drd2+ circuitry on negative emotional states.

Overall, these results contribute to a model whereby parallel, genetically-distinct BLA to ventral striatum circuits inform emotional states in a projection-specific manner.

A dollop of peanut butter and a ruler can be used to confirm a diagnosis of early stage Alzheimer’s disease, University of Florida Health researchers have found.

Jennifer Stamps, a graduate student in the UF McKnight Brain Institute Center for Smell and Taste, and her colleagues reported the findings of a small pilot study in the Journal of the Neurological Sciences.

Stamps came up with the idea of using peanut butter to test for smell sensitivity while she was working with Dr. Kenneth Heilman, the James E. Rooks distinguished professor of neurology and health psychology in the UF College of Medicine’s department of neurology.

She noticed while shadowing in Heilman’s clinic that patients were not tested for their sense of smell. The ability to smell is associated with the first cranial nerve and is often one of the first things to be affected in cognitive decline. Stamps also had been working in the laboratory of Linda Bartoshuk, the William P. Bushnell presidentially endowed professor in the College of Dentistry’s department of community dentistry and behavioral sciences and director of human research in the Center for Smell and Taste.

“Dr. Heilman said, ‘If you can come up with something quick and inexpensive, we can do it,’” Stamps said.

She thought of peanut butter because, she said, it is a “pure odorant” that is only detected by the olfactory nerve and is easy to access.

In the study, patients who were coming to the clinic for testing also sat down with a clinician, 14 grams of peanut butter — which equals about one tablespoon — and a metric ruler. The patient closed his or her eyes and mouth and blocked one nostril. The clinician opened the peanut butter container and held the ruler next to the open nostril while the patient breathed normally. The clinician then moved the peanut butter up the ruler one centimeter at a time during the patient’s exhale until the person could detect an odor. The distance was recorded and the procedure repeated on the other nostril after a 90-second delay.

The clinicians running the test did not know the patients’ diagnoses, which were not usually confirmed until weeks after the initial clinical testing.

The scientists found that patients in the early stages of Alzheimer’s disease had a dramatic difference in detecting odor between the left and right nostril — the left nostril was impaired and did not detect the smell until it was an average of 10 centimeters closer to the nose than the right nostril had made the detection in patients with Alzheimer’s disease. This was not the case in patients with other kinds of dementia; instead, these patients had either no differences in odor detection between nostrils or the right nostril was worse at detecting odor than the left one.

Of the 24 patients tested who had mild cognitive impairment, which sometimes signals Alzheimer’s disease and sometimes turns out to be something else, about 10 patients showed a left nostril impairment and 14 patients did not. The researchers said more studies must be conducted to fully understand the implications.

“At the moment, we can use this test to confirm diagnosis,” Stamps said. “But we plan to study patients with mild cognitive impairment to see if this test might be used to predict which patients are going to get Alzheimer’s disease.”

Stamps and Heilman point out that this test could be used by clinics that don’t have access to the personnel or equipment to run other, more elaborate tests required for a specific diagnosis, which can lead to targeted treatment. At UF Health, the peanut butter test will be one more tool to add to a full suite of clinical tests for neurological function in patients with memory disorders.

One of the first places in the brain to degenerate in people with Alzheimer’s disease is the front part of the temporal lobe that evolved from the smell system, and this portion of the brain is involved in forming new memories.

“We see people with all kinds of memory disorders,” Heilman said. Many tests to confirm a diagnosis of Alzheimer’s disease or other dementias can be time-consuming, costly or invasive. “This can become an important part of the evaluation process.”

Notes about this Alzheimer’s disease research

Contact: Marilee Griffin – University of Florida

Source: University of Florida press release

Image Source: The image is credited to University of Florida and is adapted from the press release.

Video Source: The video “UF researchers find that ‘peanut butter’ test can help diagnose Alzheimer’s disease” is available at the UFHealth YouTube page.

Original Research: Abstract for “A brief olfactory test for Alzheimer’s disease” by Jennifer J. Stamps, Linda M. Bartoshuk, and Kenneth M. Heilman in Journal of Neurological Sciences. Published online October 2013 doi:10.1016/j.jns.2013.06.033

Creamy or crunchy – and oh, so spreadable – peanut butter is not your first thought as a possible game-changer in Alzheimer’s disease research.

Advertisement Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

But it has potential, according to researchers at the University of Florida. They conducted a peanut butter smell test hoping to find an inexpensive, noninvasive way to detect early-stage Alzheimer’s and track its progress.

The test was conducted on cognitively normal individuals as well as:

18 patients diagnosed with probable Alzheimer’s disease.

24 patients with mild cognitive impairment.

26 patients with other causes of dementia.

The researchers found that the peanut butter test singled out those with probable Alzheimer’s.

Peanut butter smell test

Here’s how they conducted the test. The researchers asked each person to close their eyes, their mouth and one nostril. They opened a small container of peanut butter and moved progressively closer until the person could smell it. After measuring that distance, they waited 90 seconds and repeated the process with the other nostril.

In those with probable Alzheimer’s disease, the researchers had to move the peanut butter container an average of 10 centimeters closer to the left nostril than to the right nostril.

“This is a very interesting part of this study,” notes Dylan Wint, MD, a specialist in degenerative brain diseases who commented on the research. “There is a lot of research showing Alzheimer-related brain shrinkage usually starting on the left side of the brain, which is where the temporal lobe degenerates first.”

Advertisement

Ongoing research needed

The investigators, who published their study in 2013, said follow up research would be needed.

However, a follow-up study in 2014 at the University of Pennsylvania could not replicate their results. The second research team found no difference in the ability of 15 patients with Alzheimer’s to smell peanut butter in their left versus their right nostrils.

“This highlights the scientific importance of studies being repeated and refined by other researchers in different patient populations,” says Dr. Wint. “Intriguing results don’t always hold true across all study populations.”

Research continues on Alzheimer’s disease as well as on mild cognitive impairment.

A need for cheap, accurate tests

“The accessibility of current Alzheimer’s tests is one of the issues that is making diagnosis and research difficult,” notes Dr. Wint.

Currently, the most accurate early-stage diagnostic tests for Alzheimer’s are a spinal tap or an amyloid PET scan. However, these tests are expensive, uncomfortable and not available everywhere.

“The amyloid PET scan can cost $5,000, and that is just to figure out who should be studied in any Alzheimer’s study for early-stage diagnosis,” he says.

Accurate, accessible and inexpensive testing could inform more patients about their Alzheimer’s disease status. And diagnosing Alzheimer’s in its early stages is critical to finding treatments that can delay or prevent future memory loss.