Good memories beat depression 28.06.2015

Surely, many in a difficult moment of life heard advice to remember or think about something good in order to dispel longing. And surely many, following this advice, felt that depression really disappears. How and why this happens, researchers from the Massachusetts Institute of Technology led by Suzumi Tonegawa (Tonegawa Susumu) managed to find out.

The Tonegawa Laboratory has been studying the molecular and cellular mechanisms of memory for many years, and the results here have been truly outstanding. More recently, we wrote that Tonegawa, together with colleagues, managed to restore lost memories, however, so far only in mice. Among other achievements of the laboratory, one can recall experiments on the introduction of false memory and on changing the emotional sign of memories when a bad memory becomes a good one.

Memory manipulation became possible due to the fact that neuroscientists have learned to work with engram cells, which serve as a kind of "key" to the units of information stored in the brain. What's more, Tonegawa's staff has learned to distinguish which cells are responsible for which memories. In their latest work, published in Nature, they arranged for male mice to have a date with a female - memories of a good time were stored in the animals' memory, and the researchers could then activate the corresponding cells that "turned on" these memories. (The cells were supplied with a photoprotein that opened the ion channels and caused the neuron to generate a pulse, while light was sent to the mouse brain through an optical fiber.)

Then the animals were subjected to prolonged stress, which eventually led to depression. Of course, one can say that human depression is not like animal depression, but many of the symptoms of depressive states in us and in animals are similar: for example, a depressed individual, once in a difficult situation, quickly gives up and cannot enjoy what used to bring joy. This is exactly what the mice became after a long stress - but if they activated the cells responsible for good memories, then the depression miraculously disappeared, and the animals behaved as if nothing bad had happened to them lately.

At first, the depression receded only for as long as the artificial activation lasted, but if the neurons were regularly activated for five days (twice a day for 15 minutes), then the depression disappeared altogether. According to the authors, the final victory over depression required the emergence of new neurons in the dentate gyrus of the hippocampus. Animals' mood improved when the circuitry connecting engram cells in the hippocampus, the amygdala, which serves as the center for generating emotions, and the nucleus accumbens, which is often called the pleasure center, improved. Clearly, new neurons are needed to keep this antidepressant circuit active.

But maybe the bad mood of the mice could be corrected simply by giving them fresh pleasant impressions? As we have already said, with depression it is impossible to enjoy anything at all, and even if the mouse enjoyed it, its condition did not improve much. Memories of a pleasant past turned out to be the most effective. That is, attacking sadness and melancholy "outside", with the help of new "diverse and positive" impressions, by and large, is useless - depression simply will not allow them to take root in the brain and they will disappear without a trace. Memories, on the other hand, will help restore the work of neural structures, thanks to which we generally enjoy life.

New data have confirmed the correctness of those psychotherapeutic methods that try to restore joy to patients with the help of deep excursions into the past. The problem is that depression itself prevents us from thinking about something good that once happened to us. The same optogenetic trick with the artificial stimulation of pleasant memories with a person will not work, so it remains to be hoped for some kind of chemical means that could actualize a positive life experience. However, here it will be necessary to solve the problem of specific stimulation of the necessary neural circuits, and this is still the easiest way to achieve with the help of electrodes implanted directly into the brain.