They identify biological mechanisms that allow the recovery of memories

CONICET specialists discovered biological mechanisms that allow the evocation of episodic or contextual memories, those that allow recognition of a space and the experiences that took place there. The finding, described in PLoS Biology and carried out in preclinical models, could help design therapeutic strategies for Alzheimer's and other neurodegenerative diseases or to combat the natural deterioration of memory that occurs with age.

Pedro Bekinschtein (left), Magdalena Miranda, Azul Silva and Mariano Belluscio.

“A lot is known about how memories are stored and consolidated, but very little was known about what happens once those memories are stored and have to be recovered. Our work managed to describe mechanisms that allow the evocation of contextual recognition memories that constitute a type of episodic memories,” says Pedro Bekinschtein who, together with Mariano Belluscio, led the study. Both are CONICET researchers at the Institute of Cognitive and Translational Neuroscience (INCyT, CONICET-INECO Foundation-Favaloro University) and at the Institute of Physiology and Biophysics (IFIBIO, CONICET-UBA).

Bekinschtein explains that episodic memory “refers to unique experiences in our lives that have a place, a time, and other characteristic elements. In particular, we focus in this work on what is known as recognition memory, which is what allows us to decide whether a place is familiar or not when we are there. And in order to make that decision we have to be able to recover the memory of some experience that we already had in that place.”

Examples of episodic memory could be those of a person who “remembers a falafel they ate in a restaurant on a trip, the wedding of a friend, the birth of a son or daughter, a birthday in a certain place. Another example could involve returning to a place of childhood (kindergarten or school), where we may enter a room and recognize it as our own, even though there have been many changes such as colors on the walls, blackboards, drawings and ornaments. In this case, we would be evoking the memory of our living room or classroom. But it could happen that it is not completely familiar to us and we cannot evoke that old memory.”

Recovery of memories

Bekinschtein, Belluscio and the two first authors of the study, Magdalena Miranda, from INCyT, and Azul Silva, from IFIBIO, studied the evocation of episodic memory in rats that had to recognize spaces to which they had been previously exposed, but with some details ( keys) that varied over time.

“In particular, we work with rats because it is a good model to study memory and behavioral phenomena. They are mammals and their brains resemble the human brain in many ways. Many of the regions that were analyzed in our work are present in both organizations,” Bekinschtein points out.

The research team discovered that glutamate, a neurotransmitter in the hippocampus (the region of the brain where memories are formed), is key to recalling memories. “The inhibition of this neurotransmitter meant that the animals could not recognize a space they had seen. On the contrary, its activation improved their recognition capacity,” explains Miranda.

The authors of the work also focused on some hippocampal neurons known as place cells, whose identification and study earned the 2014 Nobel Prize in Medicine to John O'Keefe and Edvard and May Britt Moser.

“By carrying out experiments we discovered that differences in the activity of place cells in a region of the hippocampus called CA3 predict whether animals evoke the memory of an already experienced context or experience it as a totally new one,” says Silva. .

The results of this work can improve the understanding of memory failures in multiple neurodegenerative diseases or other types of memory deficits related to aging, says Belluscio. And he continues: “One may think that memory deficits may have to do with a failure in the storage of an experience in the brain or in the processes that keep that storage stable, but they could also have to do with failures in the retrieval of the memory. The information our study reveals could be useful in exploring strategies to preserve or improve brain health. On the other hand, the study of the biological mechanisms of memory evocation could lead to the development of specific treatments, such as, for example, to modulate the function of glutamate and thus improve the retrieval of stored information.”

Facundo Morici, from INCyT, and Marcos Antonio Coletti, from IFIBIO Houssay, also participated in the study.

Bibliographic reference:

Miranda, M., Silva, A., Morici, J. F., Coletti, M. A., Belluscio, M., & Bekinschtein, P. (2024). Retrieval of contextual memory can be predicted by CA3 remapping and is differentially influenced by NMDAR activity in rat hippocampus subregions. PLoS biology, 22(7), e3002706.

https://doi.org/10.1371/journal.pbio.3002706

By Bruno Geller