How the brain links related memories formed close in time

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If you’ve ever noticed how memories from the same day seem connected while events from weeks apart feel separate, a new study reveals the reason: Our brains physically link memories that occur close in time not in the cell bodies of neurons, but rather in their spiny extensions called dendrites.

Computer illustration of dendrites, the branch-like projections extending from neurons in the brain. Illustration Credit: Science Photo Library/Getty Images

In an article written by Emily Caldwell, from Ohio State University, she stated that discovery described in a scientific paper stems from studies in mice, in which researchers observed memory formation using advanced imaging techniques, including miniature microscopes that captured single-cell resolution in live animals.

Have you heard about dendritic compartments?
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The study shows that memories are stored in dendritic compartments: When one memory forms, the affected dendrites are primed to capture new information arriving within the next few hours, linking memories formed close in time.

“If you think of a neuron as a computer, dendrites are like tiny computers inside it, each performing its own calculations,” said lead author Megha Sehgal, assistant professor of psychology at OSU. “This discovery shows that our brains can link information arriving close in time to the same dendritic location, expanding our understanding of how memories are organized.”

The research was published in the journal Nature Neuroscience.

How we do that?
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Though most learning and memory studies have focused on how a single memory is formed in the brain, Sehgal’s lab aims to determine how we organize multiple memories.

“The idea is that we don’t form memories in isolation. You don’t form a single memory. You use that memory, make a framework of memories, and then pull from that framework when you need to make adaptive decisions,” she said.

Neurons, the principal brain cells, are known to encode and relay information. Dendrites – the branch-like projections extending from neurons – serve a critical role in how information is processed, receiving incoming information and passing it to the neuronal cell body.

Dendrites stuff
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Image taken with a fluorescence microscope showing hippocampal neurons cultured in vitro that express GFP, as well as their dendrites, which have many dendritic spines. Image Credit: Patrick Pla

But dendrites are not just passive conduits – each dendritic branch can act as an independent computational unit. While dendrites have been thought to play an important role in the brain’s function, how they shape learning and memory has been unclear until now, Sehgal said.

When mice were exposed in experiments to two different environments within a short period of time, the team found that memories of these spaces became linked. If mice received a mild shock in one of these spaces, the animals ended up freezing out of fear in both environments, associating the shock from one room with the other.

The study focused on the retrosplenial cortex (RSC), a brain region crucial for spatial and contextual memory. The researchers observed that linked memories consistently engaged the same groups of RSC neurons and their dendritic branches.

The team tracked these changes at the dendritic level by visualizing dendritic spines, tiny protrusions on dendrites where neurons communicate. The formation of new memories triggered the addition of clustered dendritic spines, a process critical for strengthening communication between neurons and facilitating learning.

Dendritic spine clusters formed after the first memory were more likely to attract new spines during a second closely timed memory, physically linking those experiences in the brain.

To confirm the role of dendrites in linking memories, the team used optogenetics, a technique that allows researchers to control neurons with light. By reactivating specific dendritic segments that had been active during memory formation, they were able to link otherwise unrelated memories, further demonstrating the importance of dendritic changes in shaping memory networks.

Memory disorders
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In addition to illuminating a previously unknown role for dendrites in linking memories, the findings open new avenues for understanding memory-related disorders, Sehgal said.

“Our work not only expands our understanding of how memories are formed but also suggests exciting new possibilities for manipulating higher order memory processes,” she said. “This could have implications for developing therapies for memory-related conditions such as Alzheimer’s disease.”

Sehgal co-led the study with Alcino J. Silva, director of the Integrative Center for Learning and Memory at UCLA, and Panayiota Poirazi, research director of the Foundation for Research and Technology-Hellas in Greece.

This work was supported by grants from the NIMH (R01 MH113071) and NIA (R01 AG013622) and from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation to A.J.S. The computational modeling work was supported by the European Commission (H2020-FETOPEN-2018-2019-2020-01, FET-Open Challenging Current Thinking, GA-863245), the National Institutes of Health (R01MH124867-01) and the Einstein Foundation Berlin to P.P. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We acknowledge resources from the Campus Microscopy and Imaging Facility (CMIF) and the OSU Comprehensive Cancer Center (OSUCCC) Microscopy Shared Resource (MSR), The Ohio State University (RRID: SCR_025078). This facility is supported in part by grant P30 CA016058 (National Cancer Institute).