Sense of smell is our most rapid warning system

The ability to detect and react to the smell of a potential threat is a precondition of our and other mammals’ survival. Using a novel technique, researchers at Karolinska Institutet have been able to study what happens in the brain when the central nervous system judges a smell to represent danger. The study, which is published in PNAS, indicates that negative smells associated with unpleasantness or unease are processed earlier than positive smells and trigger a physical avoidance response.

“The human avoidance response to unpleasant smells associated with danger has long been seen as a conscious cognitive process, but our study shows for the first time that it’s unconscious and extremely rapid,” says the study’s first author Behzad Iravani, researcher at the Department of Clinical Neuroscience, Karolinska Institutet.

The olfactory organ takes up about five per cent of the human brain and enables us to distinguish between many million different smells. A large proportion of these smells are associated with a threat to our health and survival, such as that of chemicals and rotten food. Odour signals reach the brain within 100 to 150 milliseconds after being inhaled through the nose.

Measuring the olfactory response

The survival of all living organisms depends on their ability to avoid danger and seek rewards. In humans, the olfactory sense seems particularly important for detecting and reacting to potentially harmful stimuli.

It has long been a mystery just which neural mechanisms are involved in the conversion of an unpleasant smell into avoidance behaviour in humans.

One reason for this is the lack of non-invasive methods of measuring signals from the olfactory bulb, the first part of the rhinencephalon (literally “nose brain”) with direct (monosynaptic) connections to the important central parts of the nervous system that helps us detect and remember threatening and dangerous situations and substances.

Researchers at Karolinska Institutet have now developed a method that for the first time has made it possible to measure signals from the human olfactory bulb, which processes smells and in turn can transmits signals to parts of the brain that control movement and avoidance behaviour. 

The fastest warning system

Their results are based on three experiments in which participants were asked to rate their experience of six different smells, some positive, some negative, while the electrophysiological activity of the olfactory bulb when responding to each of the smells was measured.

“It was clear that the bulb reacts specifically and rapidly to negative smells and sends a direct signal to the motor cortex within about 300 ms,” says the study’s last author Johan Lundström, associate professor at the Department of Clinical Neuroscience, Karolinska Institutet. “The signal causes the person to unconsciously lean back and away from the source of the smell.”

He continues:

“The results suggest that our sense of smell is important to our ability to detect dangers in our vicinity, and much of this ability is more unconscious than our response to danger mediated by our senses of vision and hearing.” 

How scents take on meaning

A Bochum-based research team triggered artificial odour sensations in rats – and looked at what happens in the brain as a result.

Once a scent is detected, different areas of the brain are activated. A team from the Department of Neuroscience at Ruhr-Universität Bochum (RUB) has recently discovered that structures of the olfactory sense work closely together with the brain’s reward and aversion systems. This means that scents are processed not only by the olfactory centre but also by regions responsible for emotions and valence determination. The findings were published in the journal “Cerebral Cortex”.

Dr. Christina Strauch, PhD student Thu-Huong Hoang, and Professor Denise Manahan-Vaughan from the Department of Neurophysiology collaborated on the study with Professor Frank Angenstein from the German Center for Neurodegenerative Diseases (DZNE) in Magdeburg.

Olfactory perception outside the olfactory bulb and the olfactory cortex

The researchers studied how the processing of scents affects structures in the brain. They used electrical impulses to stimulate the olfactory bulbs of test animals. Then, they analysed the activity in the olfactory cortex, where olfactory stimuli are processed. “We already knew that there is a connection between the olfactory bulb and the piriform cortex, a part of the olfactory cortex, in the perception of scents,” explains Dr. Christina Strauch, lead author of the study. “But our goal was to go deeper into the brain structures and find out which regions we had underestimated or overlooked until now.” “So far, only a few studies on olfactory perception have analysed regions outside the olfactory bulb and olfactory cortex regions in rodents,” says Professor Denise Manahan-Vaughan, spokesperson of Collaborative Research Centre 874 Integration and Representation of Sensory Processes. “It is still not completely understood how olfactory memories are formed. Our goal was to clarify to what extent brain structures that aren’t part of the olfactory system are involved in olfactory memory formation.”

Evidence of olfactory processing in the rodent brain

In their study, the researchers combined electrophysiological stimulation with functional magnetic resonance imaging (fMRI). Following this approach, the team obtained a detailed picture of the neuronal structures that responded to the stimulation of the olfactory bulb. Highly responsive structures were then analysed in more depth using fluorescence in situ hybridisation analysis of neuronal gene expression. This technique helps researchers determine whether neurons do indeed store the olfactory stimulus: This event serves as evidence of memory formation.

Sure enough, stimulation of the olfactory bulb had led to altered gene activity. This happened even in the nerve cells of the limbic cortex – that is, in a functional unit attributed with the processing of emotions. “The involvement of these non-olfactory structures probably plays a key role in the storage of olfactory experiences,” as Christina Strauch interprets the findings. “We deduce from this that rodents quickly categorise perceived scents as pleasant or unpleasant while smelling them.”

Overall, the results prove that the olfactory system works closely with the brain’s reward and aversion systems in both learning and memory formation.

“The study provides us an additional theoretical basis for understanding why the sense of smell plays such a unique role in the formation and retrieval of memories,” says Denise Manahan-Vaughan, who together with Christina Strauch has been exploring how memories are formed from scents since 2010.