Eraser for memories

aCaMKII is involved in active forgetting(Neuroscience.ru, 26.10.2008)

Article:
Inducible and Selective Erasure of Memories in the Mouse Brain via Chemical-Genetic ManipulationXiaohua Cao, Huimin Wang, Bing Mei1, Shuming An, Liang Yin, L. Phillip Wang and Joe Z. Tsien

Neuron, Volume 60, Issue 2, 353-366, 23 October 2008

Popular presentation:
Thanks for Erasing the MemoriesGreg Miller, ScienceNOW Daily News, 23 October 2008

In a study of a line of mice with induced insertion (gene knock-in) of an extra copy of the aCaMKII gene (Ca2+/calmodulin-dependent protein kinase), the role of this enzyme in memory erasure during recall (recall-induced erasure of fear memories) was shown. Plasticity of long—term memory during its recall has already been shown before; in addition, at the moment another protein kinase involved in the process of active forgetting is already known - atypical protein kinase C isoform, protein kinase M-ζ (Mzeta, PKMz). Although both the authors and commentators say something about possible practical application in the future, the obvious application of this knowledge will be the use of aCaMKII as a researcher's tool (example c PKM-ζ in this role).

Below is a detailed retelling of the article from ScienceNOW:

Scientists have learned to selectively erase memory (Kiev Media Region, 24.10.2008)

Memory is a useful thing, but partial memory is much more pleasant for many ... Why remember the bad? American and Chinese scientists managed to purposefully remove recent and long-term memories from mice without harming their nerve cells. The researchers believe that with the help of the technique they have developed, it will be possible to carry out such manipulations in humans.

A group of scientists from the Medical College of Georgia, led by Joe Z. Tsien, together with colleagues from the Normal University of East China in Shanghai, achieved the "erasure" of mouse memories by regulating the molecular mechanisms of memory.

At one time, it was proved that memory mechanisms are closely related to the activity of glutamate receptors in some nerve cells (neurons) of the brain. These receptors are located in synapses – structures that provide signal transmission between neurons. A synapse consists of a presynaptic membrane, which belongs to the cell giving the signal, a postsynaptic membrane, which belongs to the receiving cell, and a synaptic gap between them. When transmitting a nerve impulse, the "signaling" neuron secretes a neurotransmitter into the synaptic cleft – a signaling substance specific to a particular type of nerve cells. On the postsynaptic membrane there are receptors that, when interacting with this mediator, activate the receiving cell.

During the formation of memories, neurons of the corresponding brain regions secrete the mediator amino acid glutamate into the synaptic cleft, which activates the NMDA receptors of the receiving cells. Prolonged stimulation with glutamate leads to the appearance on the postsynaptic membrane of a large number of glutamate receptors of another subtype – AMPA (this phenomenon is known as synaptic plasticity). As a result, the connection between a group of neurons becomes stronger, and such an interconnected group of neurons stores a certain memory.

At one time, Qian proved these memory mechanisms by depriving genetically engineered mice of NMDA receptors, which made them unable to remember. In addition, the scientist bred a well-trained mouse, named with an increased number of receptors of this type containing the protein subunit NR2B. This subunit increases the opening time of brain "information channels". The brain of children is rich in receptors with this subunit, thanks to which large amounts of information are well absorbed at this age.

As previous studies have shown, the function of NMDA receptors is influenced by the enzyme α-calcium-calmodulin-dependent protein kinase II (aCaMKII), which is widespread in the synapses of nerve cells. It attaches to NMDA receptors, changing their properties, and thereby affects the number of AMPA receptors on the postsynaptic membrane of neurons receiving the signal.

Qian's group decided to investigate the effect of aCaMKII on memory mechanisms. To do this, they bred genetically engineered mice with increased production of this enzyme. In addition, the researchers selected a drug that suppresses its activity, which gave them the opportunity to quickly "turn on" and "turn off" the enzyme.

During the experiment, the animals were fixed with a long-term memory of a certain place where they received a small but tangible electric shock to the paw. It turned out that the animals placed in this place again "remembered" about the traumatic situation only if the aCaMKII was previously "turned off" by an inhibitor drug. If the increased activity of the enzyme was not blocked by the drug at the time of the recall, it disappeared forever, and the mice calmly reacted to the place where they received an electric shock.

A similar effect of aCaMKII on short-term memory was demonstrated in another experiment when mice were given two toys, and then the memory of one of them was "erased" in the same way. After that, the animals began to perceive it as new.

There were no side effects, as well as violations of the structure and functions of the corresponding neurons during the "cleaning" of memory.

At the current stage of development, the technique is not suitable for use in humans – the increased activity of aCaMKII was genetically implanted in mice and was suppressed by regular administration of an inhibitory drug. A possible strategy for using the method in humans is to search for drugs that increase the activity of the enzyme or trigger subsequent biochemical reactions instead.

Despite these obstacles, researchers remain optimistic about the idea of removing "unnecessary" traumatic memories. According to Qian, such a technique may in the future help people with phobias or combatants, which is especially important for the United States, where tens of thousands of people suffer from post-traumatic stress disorder after participating in military campaigns in Afghanistan, the Persian Gulf and Iraq.

However, the scientist notes that "memory cleansing" is not applicable in all cases. For example, it should not be used by people who want to get rid of memories of unsuccessful personal relationships, as the heroes of the Hollywood film "Eternal Sunshine of the Pure Mind" and other similar works did.

In any case, if the "erasure" of memories ever becomes possible, it will require a careful prediction of the consequences and the development of a solid ethical framework defining the scope of the technique, since there are plenty of obvious opportunities for abuse of it. For example, various special services, governments of totalitarian states, dishonest commercial organizations and individuals not burdened with moral principles cannot but be interested in such a development. In addition, it is not difficult to imagine the appearance of "lovers of oblivion", destroying their minds with endless attempts to get rid of absolutely all unwanted memories.

Portal "Eternal youth" www.vechnayamolodost.ru27.10.2008