Scientists teach mice to smell an odour that doesn't exist

Scientists have taught mice to smell an odour that doesn't exist in order in a study to show how the brain identifies different scents.

In experiments on mice, US neuroscientists generated an electrical signature that was perceived as an odour in the brain’s smell-processing centre, the olfactory bulb.

Because the odour-simulating signal was handmade, researchers could manipulate the timing and order of related nerve signalling like 'musical notes'.

From this, they could identify which changes were most important to the ability of mice to accurately identify the ‘synthetic smell’.

The team claims to have decoded how mammalian brains perceive odours and distinguish one smell from thousands of others.

Mice were trained to recognise synthetic odour patterns through artificially stimulated neural activity in the olfactory bulb. Left, patterns like musical notes were defined in space (top right) and time (bottom right)

NEURONS: SPECIAL CELLS THAT TRANSMIT NERVES A neuron, also known as nerve cell, is an electrically excitable cell that takes up, processes and transmits information through electrical and chemical signals. It is one of the basic elements of the nervous system. In order that a human being can react to his environment, neurons transport stimuli. The stimulation, for example the burning of the finger at a candle flame, is transported by the ascending neurons to the central nervous system and in return, the descending neurons stimulate the arm in order to remove the finger from the candle. the diameter of a neuron is about the tenth size of the diameter of a human hair Advertisement

‘Decoding how the brain tells apart odours is complicated, in part, because unlike with other senses such as vision, we do not yet know the most important aspects of individual smells,’ said study lead investigator Edmund Chong at NYU Langone Health, a medical centre in New York City.

‘In facial recognition, for example, the brain can recognise people based on visual cues, such as the eyes, even without seeing someone's nose and ears.

‘But these distinguishing features, as recorded by the brain, have yet to be found for each smell.’

The human nose is known to have 350 different kinds of odour receptor cells, while mice have more than 1,200 and therefore a more specialised sense of smell.

Past studies have shown airborne molecules carrying various scents trigger the receptor cells in the nasal cavity.

Once triggered, these receptor cells send electric signals to nerve-ending bundles in the olfactory bulb called ‘glomeruli’ and then on to brain cells, known as neurons.

This allows our brain to process odour information coming from the nose and perceive, react to and remember smells.

The timing and order of glomeruli activation is unique to each smell, much like how musical notes on sheet music are integral to a performance of a song.

Because scents can vary and mingle with others, scientists have struggled to precisely track a single smell across several types of neurons.

For the study, the research team used mice that were genetically engineered so that their neurons could be activated by having light shone on them – a technique called optogenetics.

The experiments focused on the mice's olfactory bulb, located behind the nose in both animals and humans.

The nerve fibres of smell receptor cells extend directly into the highly organised olfactory bulb, where information about odours is processed.

The mice's olfactory bulbs were exposed for optogenetic stimulation with chronically implanted glass.

Schematic of the experimental setup. Dorsal olfactory bulb was exposed by a chronically implanted 3-mm window. Stimulation patterns were projected onto the olfactory bulb of a head-fixed mouse in front of a pressure sensor for sniff monitoring, and lick spouts delivering water

They trained the mice to recognise a signal generated by light activation of six glomeruli – known to resemble a pattern evoked by an odour.

They did this by giving them a water reward only when the mice perceived the correct ‘odour’ and then pushed a lever.

If mice pushed the lever after activation of a different set of glomeruli – representing simulation of a different odour – they received no water.

Using this model, scientists changed the timing and mix of activated glomeruli.

Each change impacted a mouse’s perception as measured by their behaviour – which was defined as the accuracy with which it acted on the synthetic odour signal to get the reward.

Changing which of the glomeruli were activated first led to as much as a 30 per cent drop in the ability of a mouse to correctly sense an odour signal and obtain water.

Changes in the last glomeruli activated, meanwhile, came with as little as a 5 per cent decrease in accurate odour sensing.

Illustration of brain with olfactory bulb highlighted. The nerve fibres of smell receptor cells extend directly into the highly organised olfactory bulb, where information about odours is processed

The timing of glomeruli activations worked together ‘like the notes of a melody’ they said, and delays or interruptions in the early notes degraded accuracy of identifying an odour signal.

Control of when, how many and which receptors and glomeruli were activated let the team sift though and identify which odour features stood out.

'Now that we have a model for breaking down the timing and order of glomeruli activation, we can examine the minimum number and kind of receptors needed by the olfactory bulb to identify a particular smell,’ said study author Dmitry Rinberg at NYU Langone Health.

‘Our results identify for the first time a code for how the brain converts sensory information into perception of something, in this case an odour.

‘This puts us closer to answering the longstanding question in our field of how the brain extracts sensory information to evoke behaviour.’

The results have been published in the journal Science.