Fear memories formed before and after experiencing chronic stress can have very different behavioural effects. They also affect the brain morphology differently, finds a study. The researchers, based in National Centre for Biological Sciences (NCBS) Bengaluru came to this conclusion by studying male Wistar rats.

The researchers find that it may be possible to reverse fear memories that have been abnormally strengthened by severe stress. This is because, they find, the process of fear memory reversal itself is not impaired by stress. “This is the good news emerging from our study. Of course, these ideas need to be tested in human subjects in great detail before therapeutic relevance can be fully assessed,” says Sumantra Chattarji of NCBS in whose lab the study was conducted. The results are published in the journal Psychopharmacology.

In a pair of experiments that studied the behavioural aspects, the rats were taught to fear a 20-second-long tone of approximately 70 decibels. Later, they were subjected to a training where they were made to realise and learn that they need not fear the tone, which the scientists call as fear extinction exercise.In the first experiment, the experimental rats were subjected to chronic immobilisation stress for 10 days after which fear memories were formed. Another group was subjected to same stress for 10 days but here the fear memories were formed on the first day. The control groups in both cases were not subjected to the stress treatment and were only given the fear formation and extinction treatments.

The results showed that when fear memories were formed after stress treatment, both acquisition and overcoming the fear were impaired.

In a separate experiment, the morphological effects of stress were studied by studying eight rats. Four of these were controls and four were subjected to stress. After 10 days, the rats were sacrificed and thin slices of their brains were examined.

The researchers studied and counted the dendritic spines on specific neurons in the two sets of animals. Dendritic spines are contact points where a neuron communicates with other neurons. “We found that due to stress, the number of dendritic spines increases in the amygdale [where fear memory is formed], but decreases in the infralimbic area [where memory reversal happens] of the medial prefrontal cortex,” explains Prabahan Chakraborty from NCBS and the first author of the paper.

Effect on neurons

An increase in the number of dendritic spines is seen as an increase in the capacity of the neuron to communicate with other neurons. This strengthens the functioning of that neuron. So the above morphology experiment shows that stress acts in two ways. It not only increases the capacity of neurons involved in fear memory formation but also decreases the capacity of the neurons involved in memory reversal, thereby making it doubly difficult to erase the fear memory.

“While these results are pretty novel and add an entirely new dimension to earlier research, we feel that our findings are quite robust for several reasons,” says Dr Chattarji. According to him, an important reason is that the analysis of cells in different brain regions involved in these behaviours also undergo structural changes that are consistent with the results of the behavioural experiments.

One of the main challenges was to train the animals and execute the experiments flawlessly over a long time. “Experiments in animal behaviour are often susceptible to the finest fluctuations in something as trivial as handling the animals. Extreme care was needed to avoid unnecessary experimental confounds,” says Mr Chakraborty.