In the past, it was believed that the hippocampus is responsible for the formation of short-term memory, while long-term memories are stored in the cerebral cortex with the help of so-called biological "switches" that permanently fix important moments. However, this model could not explain why memories fade or change over time.
To investigate the process of forming long-term memory, scientists used virtual reality to make mice remember specific events. These events were repeated with varying frequency, allowing some memories to be better consolidated while others remained less stable. The team then analyzed the brain activity of the animals and applied CRISPR technology to modify genes in the thalamus and cortex, studying the impact of certain molecules on memory.
The results of the experiment showed that long-term memory is not supported by a single switch, but rather consists of a series of molecular "timers" activated at different times in various areas of the brain.
The first timers activate quickly and then fade rapidly, contributing to forgetting. In contrast, later timers activate more slowly but ensure the formation of more stable memories. The frequency of event repetitions was used to assess the significance of the information, helping to understand which memories are consolidated most effectively.
During the study, three main regulators were identified: Camta1 and Tcf4 in the thalamus and Ash1l in the anterior cingulate cortex. Camta1 provides initial memory stability after its formation in the hippocampus, Tcf4 enhances the connection between the thalamus and cortex, while Ash1l initiates chromatin remodeling processes, making memories more stable. Disruption of Camta1 and Tcf4 leads to memory loss.
Interestingly, Ash1l belongs to the family of histone methyltransferases—proteins that help preserve "memory" not only in the brain but also in other biological systems. In particular, in the immune system, they help the body "remember" past infections, and during development, they maintain cellular specialization, such as that of neurons or muscle fibers. Thus, the brain applies these universal mechanisms of cellular memory to support cognitive memories.
Understanding these mechanisms will allow for the development of new strategies for memory restoration in cases of brain damage and neurodegenerative diseases.
