Understanding the mechanics of remote memory
Memories, spanning weeks to decades, form an integral part of our identities and drastically affect how we perceive the world. ‘Remote’ memory refers to distant past memory, measured in years or even decades. It encompasses both specific memories of your own life and general memories about the past including historical events or people, almost like chapters in your autobiography. But the deciphering of very long-term, or ‘remote’, memories is still shrouded in mystery. The project RECENT-TO-REMOTE set out to explore this phenomenon. Project coordinator Inbal Goshen, a professor at the Hebrew University of Jerusalem, explains: “Only a minority of recent memories will undergo a transition to remote memory, and those are usually the most important ones, as the longevity of a memory is tightly connected to its significance. We set out to work out why.” Funded by the European Research Council, the project focused on understanding the transition of recent memories into these remote memories. The initiative aimed to understand how this process works and what it means for those dealing with memory impairment such as Alzheimer’s disease.
Remote memory connections
Key goals of the project were to study the brain cell groups involved in recent and remote memories, investigate how connections in the brain help turn recent memories into long-lasting, remote ones, and explore the role of astrocytes in memory. But achieving these goals only became possible thanks to new technologies that weren’t available when the project first started. These included tagging brain cells based on their activity to see which ones are involved in memory and monitoring astrocytic activity in mice. “Thanks to funding, we were able to upgrade our advanced microscope,” notes Goshen. “We could watch how astrocytes chronically behave in mice moving through a virtual world. We were the first to ever do this!” Astrocytes are large cells, which made it difficult in the past to see them in their entirety. But thanks to the new clear-brain techniques, it’s possible to image them comprehensively, and researchers were able to see almost 10 000 times more astrocytes than before. This study led to some exciting discoveries; that early and remote memories are similar, yet mature over time, and that astrocytes affect memory learning through targeted hippocampal connections. RECENT-TO-REMOTE also mapped the hippocampus in 3D using cutting-edge CLARITY imaging, detailing its neurons and astrocytes, and the interactions between them. The results have significantly impacted the recent field of memory research, along with the project AgeConsolidate, as evidenced by multiple publications in top-tier academic journals.
Unexpected astrocyte findings
In an unexpected twist, the researchers unearthed an important outcome they weren’t even looking for. While searching for astrocytic place cells in the hippocampus of mice that gauge location, they weren’t able to find any. But instead of throwing the research away, Goshen and her team approached it from a different perspective. They discovered that astrocytes in mice can actually signal where rewards are located, but only if they have encountered them before and not in a new environment. It’s like astrocytes have a built-in map for well-known treats. These surprising results were subsequently published in ‘Nature’. “Thanks to RECENT-TO-REMOTE findings, we now have a better understanding of the biological mechanisms underlying normal remote memory,” concludes Goshen. “So, we can start investigating diseases that have memory problems at their core, such as Alzheimer’s disease.” For both EU citizens and people worldwide, this signifies a profound leap in understanding the processes through which our brains form and retain memories. Given that our memories define us, this insight will unlock new potential in treating memory-related conditions.
Keywords
RECENT-TO-REMOTE, remote memory, memory, astrocyte, Alzheimer’s