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Where Are Pleasant Memories Stored?
March 3, 2014   
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Where do you go for a tasty bite and in which restaurants is the food not so good? Which stores offer good service and which ones are likely to leave you hopping mad?

For every human being, but also for animals, information about pleasant and unpleasant experiences is of key importance. Researchers from the Nencki Institute of Experimental Biology in Warsaw have discovered how and where pleasant memories are stored.

The researchers have shown that pleasant memories are stored in an area of the brain known as the central nucleus of the amygdala. The results obtained by a group of researchers led by Prof. Leszek Kaczmarek and Ewelina Knapska, Ph.D., which have been published in The Journal of Neuroscience, show that just one protein plays the key role in the process of memorizing pleasant experiences. In the future these results may help in finding more effective ways of treating addictions, depression and schizophrenia.

“In our research we are striving to understand the relation between the mind and the brain by studying memory, which is of fundamental importance for the mind. Without memory there is no mind,” says Kaczmarek.

Neurobiologists differentiate between many types of memory, the most basic types of which are characterized by clear duality. For example, we have short- and long-term memories, and declarative and procedural memory (declarative memory refers to events and data, while procedural memory is the memory of actions). The researchers at the Nencki Institute have focused on another dichotomy of great importance to every human being and animal: on appetitive memory—related to memories of pleasant experiences, and on aversive memory—related to unpleasant experiences.

Experimental research on human memory often comes up against a basic problem: there are no volunteers for experiments. No one of sound mind will agree to participate in experiments that may erase parts of his or her memory. Fortunately, having a mind is not limited to humans. Many mental activities typical for humans also take place in the minds of animals. Therefore the scientists at the Nencki Institute conducted their experiments on mice placed in so-called intelligent cages. In each corner of the cage two water bottles are placed. In order to get the water, a mouse has to get to the corner and press on a small flap on a bottle with its nose. Depending on the type of experiment, the mouse will get either water or a harmless but unpleasant puff of air on the nose. All mice in the cage have individual ID chips and therefore researchers are able to tell exactly what decisions are made by each mouse.

The intelligent cage makes it possible to conduct a variety of experiments. If, for example, in one corner of the cage bottles with sweet water are placed, the effectiveness of spatial memory in mice can be investigated. More subtle experiments are also possible by placing only one sweet water bottle in a selected corner. Then the mouse needs to remember not only the corner where the sweet water bottle is, but also which of two bottles contains sweet water.

Twenty-five years ago Nencki Institute researchers observed changes in the activity of a gene known as c-fos in the nervous cell nuclei during learning. One protein whose production is regulated by a protein encoded by the c-fos gene is the MMP-9 enzyme active outside of the cell. The researchers decided to investigate the role of MMP-9 in memorizing pleasant and unpleasant experiences. In order to do this, they conducted a series of experiments on control mice and on mice either lacking this protein entirely or with its selective blocking only within the central amygdala. The amygdala is a small structure within the cerebral hemisphere and it is located at the base of the brain, close to the hippocampus. It consists of two groups of nuclei responsible for innate and acquired emotional reactions, such as laughter or fear.

The researchers were surprised by the experiments. When placed in the intelligent cages, the control mice after three days of learning almost always chose the corner with sweet water. Mice lacking MMP-9 behaved differently: they showed no preference for any of the corners. At the same time, all the mice were equally good at remembering the corner where they received the unpleasant puff of air on their noses. Furthermore, selective blocking of MMP-9 just in the central amygdala produced the same effect—the memory for the sweet water location could not be formed.

“The results are clear: Pleasant experiences are memorized due to changes in plasticity within the neurons of the central nucleus of the amygdala,” says Kaczmarek. “We have shown that just one protein, the MMP-9, is responsible for learning about pleasant experiences and memorizing them. At the same time, this protein has no impact on the memory of unpleasant experiences.”

These research findings help explain the processes of learning and appetitive memory by referring to two seemingly distant domains of neurobiology: system neurobiology—investigating entire neuronal structures (such as the central nucleus of the amygdala), and molecular neurobiology—investigating physical and chemical processes responsible for various functions of nervous cells (in which the MMP-9 protein takes part).
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