New research opens the door to understanding neural mechanisms of learning using odours

A team from IBioBA published a research paper in the journal Nature Communications in which they identified that learning modifies the way the olfactory cortex processes odours. This paper changes the paradigm in which information processing in the brain was understood.

A smell that takes you back to your childhood, the perfume that reminds you of a loved one, your favourite food, the summer house you always want to return to. Smell is undoubtedly much more than just smelling smells. Through smell, people are able to detect and recognise a large number of chemical compounds in the environment, which influences their memory, emotions and behaviour. And despite being a fascinating sensory capacity, it is one of the least understood.

“Smell is still very enigmatic. Much more is known about how sight works, how hearing works, taste or touch, but not smell”, says Noel Federman, a researcher at IBioBA with expertise in the study of learning and memory. “In the lab, we study sensory perception, using olfactory perception in mice as a model”, she says.

In 2017, in the Neural Circuits lab led by Antonia Marin-Burgin, they wondered whether the perception of sensory signals depends on the context in which they occur. After many years of work, experiments and scientific discussions, they managed to translate their research into a paper published in the prestigious journal Nature Communications. There, they argue that learning favours odour discrimination in the olfactory cortex, since, by incorporating information from different senses, it improves the processing of odours and their relevance to the environment.

By observing the behaviour of mice and analysing their neural activity, the team was able to see that, while initially this region only encodes odours, “after learning, the neurons start to respond to positional, contextual and associative cues as well, becoming activated by more than one type of stimulus, which is called mixed selectivity. This means that, in addition to odours, they now also encode additional information, for example about the environment where the odour occurred”, Marin-Burgin explains. This integration of non-olfactory signals in an olfactory zone allows odour-environment-reward associations to be stored in the same region, which leads to a better distinction of odours when they occur in the same environment. “It’s as if I can distinguish the smell of my grandmother’s food better when I smell it in her house than when I smell it in a restaurant where I don’t expect to smell it”, he says.

“That is, we discovered that there are neurons in the olfactory cortex that respond to aspects other than odour, such as visual stimuli, and the value of stimuli, such as receiving a reward. So it is likely that the olfactory cortex is involved in changing the perception of the same odour in two different contexts”, Federman reinforces.“The olfactory cortex does more than just smell: it integrates things, and by integrating things, it could be helping learning, because learning is integrating two or more pieces of information”, adds Sebastián Romano, a CONICET assistant researcher at IBioBA and one of the first authors of the paper.

This research is important because several scientific studies claim that a reduced ability to smell can be an early symptom of diseases such as Alzheimer’s or Parkinson’s: “there are many neurodegenerative and even viral diseases in which loss of smell is one of the first symptoms, so understanding the neural circuits associated with odour processing can provide new knowledge for the development of potential treatments”, says Marin-Burgin.

A capricious perception

This is how Noel Federman describes it when he explains that perception is changeable and that this versatility depends on learning and context. “When we are hungry, for example, we perceive smells more intensely or more quickly. It is interesting to have a brain that is able to focus attention on stimuli that are relevant depending on the task we want to perform. For example, if we are hungry and we are looking for food, then it is very important that we can pay more attention to stimuli that indicate food and ignore those stimuli that don’t”, says the researcher.

According to Antonia Marin-Burgin, associations, which are memory-forming, are located in different parts of the brain and have to do with the environment: “the context in which we find ourselves helps us to better interpret – in this case the smell – what is being perceived, and this information is stored in the sensory cortex”, she says.

A brain that works collectively

“We saw that information is much more distributed in the brain, not compartmentalised as previously thought”, says the head of the lab. Traditionally, the brain was understood to work in a hierarchical way: brain regions that are particularly sensory-oriented inform regions of a higher ‘hierarchy’ to integrate information. “This idea is beginning to be questioned -says Sebastián Romano- and our work shows it in a very clear way: we were able to see that in what would be the first stage of sensory processing, which in this case is olfactory, where the information is still very primitive, there is already an integration of many sensory modalities: of the animal’s behaviour, of the rewards it receives. So we saw that the brain is much more integrative from the start”.

This work, then, makes clear a point about brain function that has long been discussed but not yet described: the brain integrates information from the earliest stages of processing. “The brain processes the information it receives from the environment in a more collective and distributed way, it is not the top-down brain we thought it was”, adds the researcher.

Those who also worked collectively were the members of the Neural Circuits lab. “This represented a very nice ambition because we did something from scratch and I think we were able to achieve it because we are people with different backgrounds who contribute a lot”, says Federman. “We were very lucky to find each other because we have very different and very complementary profiles. It would be very unlikely that anyone could have put all this together alone”, agrees Romano. Both also stress that the research would not have been possible without the contribution of doctoral fellows Lucca Salomon and Macarena Amigo Durán. It should also be noted that the work was carried out entirely in Argentina, and that it was led by a female scientist.