Artificial recreation of happy memories may become the next big weapon against depression

Urging a depressed person to stay positive by remembering the good things in life is unlikely to be helpful advice. That is because depression blocks access to happy memories. But what if we could somehow artificially recreate such memories to allow for some more positive thinking? A study suggests that this is indeed possible – at least in rats.

Surprisingly, the psychology and physiology of rodents is not so distant from our own. And if the same effect could be observed in humans, it might help open depressed individuals up to positive general interpretation of life experiences that make it possible to lift the dark veil of depression.

The brain and depression

Clinical depression, which is different from a temporary bout of sadness, is a rather common psychopathological disorder characterised by persistent negative moods, feelings of sadness, loss of interest and motivation. It has negative consequences on sleep and affects many aspects of an individual’s life, including what would otherwise be rewarding behaviours – like eating.

In humans it affects both adults and children, but general behaviour consistent with depression can be observed in animals. This has limits of course. For example, human depression is characterised by hopelessness and suicidal thoughts, which cannot be detected in animals. However, loss of interest is present in both. In rodents, more specifically, loss of interest can be easily detected by measuring sucrose preference – depressed animals lose interest in sugar.

Animal models for depression are extremely helpful in trying to understand biological, physiological and genetic bases of this pathology. The new research does shows that the artificial reactivation of brain cells spontaneously active during positive experiences, substantially decreases depression (anhaedonia) in rats.

A cross-section of a positive memory. Seen here is the hippocampus; the brain cells glowing in red were previously active during the encoding of a positive memory.Credit: Steve Ramirez

The researchers used a method called optogenetics, in which specific brain cells are genetically sensitised to light and then activated using pulses of light, in the experiment. Light-sensitive molecules were in this way used to detect which brain cells were activated by a certain experience in the animals. The area of the brain chosen by the researchers to be tagged by these molecules is the hippocampus, more specifically a subarea of the hippocampus called the dentate gyrus. This is linked to the formation of memories and to responses of avoidance and of appetite, and thus records positive and negative experiences.

The researchers first induced anhaedonia in male rodents by exposing them to repeated stress by making it impossible for them to move, such as hanging them by the tail. They then exposed them to three types of experiences: positive (being put in a cage with a female), negative (being immobilised in a cage) or neutral (being put in an empty cage) and recorded which brain cells were active during these experiences.

Mmmm at least three sugars in this one.Lori Leaumont/Flickr, CC BY-SA

The researchers then used pulses of light to activate the cells they had pinpointed. They found that only the reactivation of cells in the dentate gyrus that were active during positive experiences (but not the reactivation of those active during negative or neutral experiences) made rats show interest in sugar again, meaning they had been relieved from depression.

Next steps

What’s so interesting about this, particularly for a memory researcher, is that it was the artificial reactivation of the cells (the reactivation of the positive memories) and not re-exposure to these positive experiences that did the trick.

In other words, being put again in a cage with a female did not lift the rats from depression. One can speculate that being put again in a cage with a female does not necessarily reactivate a memory, as it can be encoded as a new experience. It seems, then, that it is the reactivation of the neural network linked with a positive past experience, and not the positive experience in itself, that helps.

But can these results be extended to humans as they are? Not immediately, of course. However there is hope, as for example clinical studies have shown that therapeutic cognitive-behavioral interventions using positive mental imagery or the restructuring of how past experiences are interpreted, might be of help. The link between personal memories and depression is also currently experimentally investigated.

Crucially, what this study shows is that it might be indispensable in treating depression in humans to use an external and artificial trigger to unblock the access to positive memories. Optogenetics is already starting to be used in humans, but with great caution, as it can require implants. But it is not inconceivable that these external and artificial triggers could be light pulses in the future.

Either way, an important building brick has been laid that helps not only to understand how depression works, but also how it can be treated. However, more research will be necessary to obtain a clearer picture of how this might work in humans.

Giuliana Mazzoni received funding from the ESRC and the British Academy in the UK.