Creating memories

A new line of genetically modified mice allowed scientists at the Scripps Research Institute, working under the direction of Dr. Mark Mayford, to identify cellular contacts formed during the memorization process. By tracking a protein labeled with a fluorescent green label as it moves through individual neurons, from the cell body along the dendrites branching from it, scientists were able for the first time to determine exactly which types of synapses are involved in the process of teaching animals fear of electric current.

Neuroscientists are of the opinion that in the process of memorization, in response to the impact of certain stimuli, there is an increase in individual synaptic contacts. It is most likely that this amplification is the result of migration of certain proteins into the synapse zone, occurring in a strictly defined sequence. However, it is still unknown what kind of proteins they are and how their movement is carried out.

The first "tracked" protein was a receptor for glutamate, a neurotransmitter whose role in the memorization process was established earlier. To do this, scientists have created a line of mice in whose body, under strictly specific controlled conditions, the glutamate receptor begins to emit a green glow.

These mice were trained to expect an electric current to affect the paws when placed in a certain container. According to Mayford, the resulting fear is a very stable long-term memory. Presumably, the neurons activated during the development of the fear of an electric shock container are responsible for the formation of the conditioned reflex of disgust.

The fluorescent receptor was modified in such a way that neurons began to synthesize it only when they switched to the active state. This allowed the authors to identify the nerve cells involved in memory formation.

On mouse hippocampal slices obtained 1, 2 and 6 hours after animals were exposed to electric current,
it can be seen how glutamate receptors (green dots) migrate along dendrites. The bodies of neurons are shown in blue.

In addition, scientists could completely disable the fluorescent protein synthesis system using the drug doxycycline. Throughout their lives, doxycycline was added to the diet of mice, taking a break only for the period of the experiment. Thus, the labeled protein was synthesized exclusively during the formation of a certain memory.

The study of brain tissue slices taken at different points in time from the beginning of the experiment allowed the authors to trace the migration of glutamate receptors from the site of synthesis to the hippocampus region of the brain. The protein synthesized in the nuclei of the involved neurons traveled along small branching processes of cells – dendrites – and eventually settled in sufficiently distant synapses.

Synapses are of several types, depending on the shape of the processes forming them: thin, thick or mushroom-shaped. An interesting fact is that glutamate receptors mainly accumulated in synapses of the same type formed by mushroom-like processes of neurons (with such an increase, as in the above images, individual synapses, unfortunately, are not visible).

This fact indicates that, at least, in the process of forming a fear-related memory, a specialized system is involved that directs the movement of synaptic proteins into certain cells. However, it is not yet known which molecules are involved in this.

Another mystery is that the labeled receptor disappears from synapses within 72 hours, while the memory persists much longer. Undoubtedly, other proteins and regions of the brain are also involved in the formation and maintenance of memory. Obviously, the hippocampus is not the final place to store information about the fear of a certain factor. The authors suggest that it stores information about the "place" of the memory, in this case, the container in which the "training" was conducted. And the role of preserving the fear of electric shock is performed by the so-called amygdala.

As part of earlier experiments to study the activity of the amygdala in the same line of mice, the authors found that the activation of the same neurons occurs both during the formation of a memory fragment and when returning to it. In the near future, they plan to apply a new, more precise approach to the study of memory formation in the amygdala.

Another idea is to use a new technique to find out the exact structure of the memory that forms in the hippocampus, in particular, memories of a container beating with an electric current. Mayford plans to find out if it is possible to teach a mouse to be afraid of a container, which was put in a container, but not subjected to electric shocks inside it. To do this, he is going to activate the hippocampal neurons that store the memory of the container, and then expose the animal to current.

If this experiment is successful, its results will help explain the mechanism by which the container is displayed in the mouse brain, and bring scientists closer to solving one of the main questions of neuroscience: how the brain displays the external environment.

Evgeniya Ryabtseva
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of TechnologyReview 

26.02.2008