Biologists cured mice of fears by neuronal transplantation

Sofia Dolotovskaya, N+1

Chinese scientists have shown that the transplantation of embryonic (in fact, as can be seen from the picture, here and further it should be read "fetal" – VM) neurons into the amygdala of mice makes it easier for them to get rid of fears. Article Yang et al. Fear Erasure Facilitated by Immature Inhibitory Neuron Transplantation is published in the journal Neuron.

Here and below are the drawings from the article in Neuron.

Generalization of fear and inability to get rid of traumatic memories lead to the development of post-traumatic stress disorder and other fear-related mental disorders. Both behavioral and pharmacological therapies are used to treat such disorders in humans. However, despite the fact that many of these treatments are very successful at first, a significant proportion of patients with serious disorders relapse after a while.

The same phenomenon has been described in rodents. Mice taught to be afraid of a certain sound – due to the fact that it was accompanied by electric shocks during the learning process - can be cured of traumatic memories during the so–called "fear attenuation". If the mice repeatedly hear the same sound, not accompanied by electric shocks, the fear gradually fades. However, often the fear spontaneously returns if the mice hear this sound some time later.

Interestingly, in young mice, such a spontaneous return of fears does not occur during a certain critical period. At the same time, the end of this critical period coincides with the moment of formation of perineuronal networks in the brain – the extracellular matrix surrounding synapses. Previous studies have shown that the pharmacological destruction of perineuronal networks around the inhibitory neurons of the amygdala (a structure that plays a key role in the perception of emotions and fears) leads to the disappearance of the spontaneous return of fears. Based on this, the authors suggested that the "rejuvenation" of the amygdala neurons may lead to the same effect.

To test this assumption, scientists decided to transplant embryonic neurons into the amygdala of adult mice, from which mature neurons of this brain structure are formed during development.

As a control, groups of mice were used, to which dead embryonic neurons were transplanted. After transplantation, mice from both groups formed a fear of a certain sound. For different subgroups of mice, fear formation was carried out 7, 14, 21 or 28 days after transplantation. After the mice got used to being afraid of sound, the authors caused them to fade out of fear, which lasted for two days. Then, a week later, the researchers played the scary sound to the mice again and looked to see if they would have a spontaneous return of fear.

The scheme of the experiment.

It turned out that in mice with transplanted live embryonic neurons, the spontaneous return of fear occurred three times less often than in mice from the control group. At the same time, such an effect was observed only for those mice in which fear was formed two weeks after transplantation. In all other subgroups, fear returned at least as often as in the control group.

The authors also conducted an additional experiment in which they checked whether the transplantation of embryonic neurons of the amygdala helps to get rid of old fears for good. To do this, neurons were transplanted after the formation of fear in mice. However, it turned out that such mice, having heard a terrible sound after transplantation, still continued to be afraid of it. But at the same time, the attenuation of fear subsequently took place in them much more effectively, and the spontaneous return of fear was observed less often than in the control group mice.

Histological analysis of the amygdala helped explain why the effect of the disappearance of the spontaneous return of fear was observed only two weeks after the transplant, but not earlier and not later. It turned out that the transplanted neurons eventually go through all the stages of maturation they are supposed to and form functional synapses with existing neurons. Transplanted cells cause a decrease in the synthesis of perineuronal networks and, apparently, as a result, increase the synaptic plasticity of amygdala neurons. At the same time, a noticeable number of synapses are formed about two weeks after transplantation, when the transplanted neurons are represented by a mixture of mature and immature cells. A week after the transplant, the number of new synapses is still very small, and the transplanted neurons are mostly immature. And 3 and 4 weeks after the transplant, the neurons, on the contrary, are already "too mature".

The authors hope that in the future the results obtained may help in the treatment of phobias and post-traumatic stress disorder in humans.

Portal "Eternal youth" http://vechnayamolodost.ru  12.12.2016