Sudeshna Das (left) and Madhumala K. Sadanandappa

Ever noticed how that fusty smell which hits you when you walk into a room locked up for days becomes bearable within a few moments? Or how the strong, sweet smell of a flower fades as you keep sniffing it?

Most of us usually pay no thought to these things. For scientists however, these phenomena present the opportunity of a lifetime — to understand how the brain processes sensory inputs it receives and turns them into building blocks of cognition.

Researchers have known for a while about this ubiquitous psychological phenomenon in which constant exposure to a stimulus results in a weakened response. But they were clueless how the process they call habituation plays out in the brain.

That is the puzzle Veronica Rodrigues wanted Sudeshna Das and Madhumala K. Sadanandappa to crack for their PhD. The two joined Rodrigues’ lab at the National Centre for Biological Sciences (NCBS) in Bangalore in 2008 as doctoral students. Rodrigues, a neurobiologist specialising in the perception of smell, died last November following a prolonged battle with breast cancer.

Her students, however, have carried forward her legacy. After three years of hard work the two scholars, together with counterparts from Ireland, Japan and the US, have not only cracked the code but also worked out the minutest genetic mechanisms in great detail. Apart from Rodrigues, they were guided by Mani Ramaswami of the Trinity College Institute of Neuroscience (TCIN) in Dublin, who is also an adjunct professor at NCBS.

Using the fruit fly (Drosophila) —whose brain is similar to that of mammals but less complex — as a model, the scientists discovered that continuous exposure to a smell causes the brain cells that receive the signals from the antenna (nose) to show a reduced response. This reduction is not because sensory cells in the antenna do not respond to smell. It is because after habituation brain cells that respond to this specific smell begin to receive strong inhibitory signals from another group of brain cells.

The experiments, conducted combining genetic and anatomical techniques with high-speed brain imaging, revealed unexpected and interesting ways by which the inhibitory signal grows stronger, and how this in turn leads to structural and genetic changes in the brain.

Habituation is of fundamental importance to the learning process. It serves the vital purpose of filtering out prolonged sensory inputs so that the brain can focus its cognitive resources on new stimuli coming its way, says Ramaswami.

The findings, which appeared in two different papers in the journal Proceedings of National Academy of Sciences last week, are not without clinical significance. They may help scientists get to the bottom of hyper-reactivity found in people suffering from several neurological disorders, including autism spectrum ones.

The work is important for other reasons as well. Ramaswami says it is for the first time that scientists have been able to understand the mechanism of habituation associated with any sense in great detail. Hence, this study could pave the way for comprehending the habituation process in other, more complex senses such as vision, hearing, taste and touch.

The scientists also found that sensory cells involved in habituation vary from smell to smell. “For instance, when the insects were exposed to one smell, they became habituated to that particular smell but not to other smells to which they had not been exposed. It implies that habituation is stimulus specific,” says Das, the Calcutta girl who joined NCBS after her postgraduation from Calcutta University.

Just like short-term and long-term memory, habituation is also of two types. The experiments with fruit flies have shown that short-term habitation kicks in when the insects are exposed to a smell constantly for 30 minutes, but for long-lasting habituation to happen, the exposure needs to be extended to four days. “The reduction in the sensory perception to that particular smell remains intact for 45 minutes and six days, respectively, after the exposure is withdrawn,” says Sadanandappa.

The second paper, to which foreign collaborators from TCIN and the University of Arizona, the US, contributed, has shown that a gene called Ataxin-2 is crucial for long-term habituation. This discovery is important because the same gene is also implicated in a neurological disorder called spinocerebeller ataxia type 2, a progressive disorder which affects gait and is often associated with poor coordination of hands, speech and eye movements.

Besides, understanding habituation is also important for deciphering the phenomenon of “dishabituation”, says Ramaswami. “There are times when it is important to dishabituate, or suddenly pay keen attention to what was a boring background. For instance, when a tiger snarls in the forest, every blade of grass draws your attention,” he says. Such stimuli may work in part by blocking the inhibitory signals that lead to habituation and thus restore the brain to its original or enhanced, behavioural state, he observes.

This study definitely smells like a winner!