The human brain is swamped by information from the five senses every waking minute. A normal brain dismisses most of these inputs, retains a fraction of them for a few hours and commits a still smaller portion to long-term memory. If the brain did not discard the unnecessary information, it would become cluttered and it would be difficult to retrieve memories or important information, for example the name of a new colleague.

But how exactly does the brain purge irrelevant information? Neuroscientists have been trying to figure that out for a long time. While they have some clue about the neural processes involved, they are still a long way away from satisfactorily explaining how the brain purges memories.

A team of researchers at Bangalore's Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) has, along with their counterparts in France, moved a step closer to the solution. They have identified the key role played by a gene in purging unwanted memories. Their work was reported in the latest issue of Journal of Biological Chemistry.

The JNCASR researchers, led by biochemistry professor Tapas Kumar Kundu, found that mice that are born without the PC4 gene in their brain never forget what they have once learnt. The mice were given a reward at a certain spot. They kept on going back to that spot even when the reward was removed. This indicates that they were unable to overwrite the new information (absence of reward) on their original learning.

This comes close on the heels of researchers from the University of Oxford and the University College London coming up with the concept of 'anti-memories'. New electrical connections are formed between neurons when new memories are created. Naturally, this excites the neurons and disturbs the excitability / inhibitory balance of the brain. To correct the balance - the scientists demonstrated through animal experiments and mathematical modelling - the brain creates the exact opposite electrical pattern (of the memory). These are called anti-memories and have a hand in suppression of memories.

This landmark study appeared in the journal Neuron last month.

"Memory extinction (the process by which old memories are replaced with newer experiences) is an essential physiological function of the brain, which makes our life easy by allowing us to learn new things, and erase irrelevant day-to-day incidents," Kundu told KnowHow.

"Extinction forms a central dynamic component of memory along with acquisition, consolidation, retrieval and reconsolidation. These are governed by overlapping but independent processes and are not binary opposites of one or the other," says Aurnab Ghose, associate professor of neurobiology at the Indian Institute for Science Education and Research in Pune. The importance of extinction in memory (and its implications on mental health) should thus be seen in the context of multiple dynamic processes that constitute memory.

According to scientists, what happens during memory extinction is not erasure of the original memory. Instead, both old trace of memory (reward was kept there, in this case) and a new memory (that reward has been removed) compete with each other. In normal mice, the new memory wins out.

"Getting over old memories is as important as forming new ones," says Amrutha Swaminathan, Kundu's doctoral student who carried out the experiments. Traumatic conditions, such as accidents or victimisation, affect normal people psychologically and trigger post-traumatic stress disorder (PTSD) in at least some of them, she says. Since the absence of PC4 in the brain - as shown in the mice experiments - leads to a problem in memory extinction, measuring the amount protein produced by the PC4 gene in the human brain could give an indication of how easy or difficult it would be for a person to overcome stressful situations.

Kundu's lab has been studying the PC4 gene for more than a decade. The earlier work had shown that this gene is an integral part of chromatin - the material in the nucleus of a cell that condensates to make chromosomes - and its absence would make the genome completely disorganised. Kundu's earlier PhD student Chandrima Das, currently an associate professor at the Saha Institute of Nuclear Physics in Calcutta, was the first one to identify the gene's connection in the brain many years ago.

The new set of experiments, however, took the understanding much further. Interestingly, the scientists found that the mice that lacked the PC4 gene in the brain were smaller and quieter than their normal counterparts.

This study has shown for the first time "how proper chromatin organisation could be important for the process of memory extinction," says Kundu.

According to him, the experiments showed that these mice produced fewer new neurons in their brains, and this could probably explain their brain defect.

PC4 has a vital role in the genome dynamics of the brain as it influences the functioning of many genes, says Kundu.

Apart from PTSD, the new findings may have other potential therapeutic applications. It might help extinguish fear memories, an experiment that they intend to carry out in mice in the next stage. It may be similarly useful in treating drug addiction. "Extinction of the in initial coupling of the good feeling associated with the drug is essential to overcome addiction," says Amrutha.

We now have to wait for the studies to be replicated in humans.