Several areas of the brain are involved in the gradual restructuring of memories into long-term forms.
A recent study has shown that long-term memory is created through a chain of molecular "timers" that are activated in different areas of the brain. Using a behavioral model with virtual reality on mice, researchers found that key regulators either strengthen memories, turning them into more stable forms, or suppress them until they fade away. The results, published in the journal Nature, emphasize that several brain regions are involved in the gradual restructuring of memories into long-term forms, with mechanisms that assess the importance of information and promote its retention.
For a long time, memory research focused on two key areas of the brain: the hippocampus, responsible for short-term memory, and the cerebral cortex, where long-term memory was thought to be stored. Scientists had hypothesized that long-term memories are controlled by biological "switches." Under this model, if short-term memory was marked for transfer to long-term memory, it would be preserved indefinitely. However, despite numerous discoveries, it became clear that such a scheme is overly simplistic.
The researchers published a paper describing a neural pathway linking short-term and long-term memories. The thalamus plays an important role in this process – an area in the center of the brain that not only helps determine which memories are worth retaining but also directs them to the cortex for long-term stabilization. These findings pave the way for answers to fundamental questions about memory: what happens to memories after short-term storage in the hippocampus and what molecular mechanisms determine which memories transition to long-term storage and which are forgotten.
To study these processes, the team created a behavioral model using virtual reality, in which mice formed specific memories. By varying the frequency of certain events, the researchers achieved better memory retention for some things compared to others, and then examined the brain to determine which mechanisms were responsible for the longevity of these memories.
However, simple correlations were not enough. To prove causality, the team also created a CRISPR platform for gene manipulation in the thalamus and cerebral cortex. Using this, the scientists demonstrated that the removal of certain molecules alters the duration of memory. Each molecule affected different time scales of memory.
The results show that long-term memory does not depend on a single molecular "switch," but is supported by a cascade of genetic programs that are activated at different times and in different areas of the brain, similar to a series of molecular timers. The first timers activate quickly and fade rapidly, facilitating quick forgetting; later ones activate more slowly but create more durable memories. This staged process allows the brain to retain important events for a long time, while less significant ones gradually fade away. In the study, the importance of memories was assessed through repetition frequency: events that occurred more often were remembered better.
The scientists identified three transcription regulators: Camta1 and Tcf4 in the thalamus and Ash1l in the anterior cingulate cortex. These molecules are not necessary for the initial formation of memories but are critically important for their maintenance. Disruption of Camta1 and Tcf4 impairs the connection between the thalamus and the cortex, leading to memory loss.
According to the model, after the formation of basic memory in the hippocampus, Camta1 and its targets provide initial stability for memories. Later, Tcf4 and its targets are activated, maintaining cellular structure and connections between neurons. Ultimately, Ash1l initiates chromatin remodeling programs, making memory even more resilient.
<iframe width="560" height="315" src="https://www.youtube.com/embed/1lDos0P36xA?si=zpD856V4IcdyYC8-" title="YouTube video player" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share" referrerpolicy="strict-origin-when-cross-origin" allowfullscreen></iframe>
