Consultant instance of backbone dynamics throughout longitudinal imaging displaying clustering of latest spines following linked reminiscence formation. Credit score: Nature Neuroscience (2025). DOI: 10.1038/s41593-025-01876-8
Previous neuroscience research recommend that recollections of occasions that occurred at brief time intervals from each other are sometimes linked, through a course of known as reminiscence linking. Whereas reminiscence linking is now a well-documented phenomenon, its neural underpinnings haven’t been absolutely elucidated.
Researchers on the College of California Los Angeles (UCLA) lately carried out a examine geared toward higher understanding the neural processes that contribute to reminiscence linking within the mouse mind. Their findings, printed in Nature Neuroscience, recommend that dendritic plasticity, the difference of dendrites (i.e., branch-like extensions of neurons) over time, performs a key position within the linking of recollections.
“A few years back, in a landmark study published in Nature in 2016, we demonstrated that memories formed a few hours apart are linked because they are stored in a common set of neurons in the hippocampus,” Alcino Silva, senior writer of the paper, informed Medical Xpress. “We wanted to know: Where within these neurons are these memories stored and linked? What was causing these neurons to be recruited?”
Whereas answering these analysis questions in an experimental setting was unfeasible just a few years in the past, since then Silva and his colleagues have developed new instruments and applied sciences to probe subcellular mechanisms. In collaboration with Yiota Poirazi’s laboratory on the Basis for Analysis and Expertise in Crete, they then got down to examine how dendritic and synaptic dynamics may contribute to reminiscence linking, using modeling methods.
“In an earlier theoretical study also published in 2016, we predicted that in addition to being stored in common neuronal populations, linked memories should also reside within common dendrites within these neurons,” stated Poirazi.
“Inspired by these findings and with the help of our multidisciplinary team, we set out to reveal whether and how dendritic mechanisms may allow the linking of memories across time in rodent brains,” added Silva.
As a part of their latest examine, the researchers employed three completely different however complementary imaging methods. Utilizing these methods, they visualized three distinct subcellular compartments in dwelling mice, specifically the soma, dendrites and spines from neurons.
“We showed that when mice form two memories close in time, we can see that many of the same somas, dendritic branches, and spines are involved in forming these two memories,” defined Megha Sehgal, the primary writer and a co-corresponding writer of the paper.
“In a second class of experiments, we used sophisticated genetic tagging techniques to manipulate these neuronal somas and dendrites. When we forced independent memories to be stored in the same neuronal somas or even the dendrites and found just this simple intervention in one brain region, the retrosplenial cortex, was enough to link these memories!”
Silva, Sehgal and their colleagues discovered that, following their experimental intervention, mice turned afraid of a field that was beforehand unimportant to them, just because the reminiscence of this field was saved in the identical dendrites that saved recollections of a field wherein they skilled an electrical shock. In collaboration with Poirazi and her lab, they then used computational modeling methods to elucidate their observations.
“By simulating a bio-realistic network of neurons with dendrites and localized plasticity, the model showed that localized dendritic plasticity mechanisms are necessary for replicating key properties of linked memories, such as their recruitment of the same dendrites, clustering of synapses, and stability over time,” stated Sehgal.
Consultant RSC pictures of cFos-tTa mice injected with TRE-hChR2-mCherry-DTE and TRE-hChR2-mCherry displaying selective expression of Channelrhodopsin in dendritic segments within the presence of DTE. Credit score: Nature Neuroscience (2025). DOI: 10.1038/s41593-025-01876-8
The findings gathered by this analysis group recommend that the linking of recollections within the mouse mind is supported by extremely localized modifications (i.e., inside just a few micrometers) on neuronal dendrites. Silva, Sehgal and their colleagues hypothesize that related localized dendritic modifications may additionally play a job in different kinds of reminiscence processes.
“Although such localized changes have been reported in previous studies in cell cultures and brain slices, we did not know their function,” stated Sehgal. “To the best of our knowledge, this is the first demonstration of their usefulness in animal behavior.”
This latest examine may quickly pave the way in which for additional analysis exploring the contribution of dendritic plasticity to particular well-documented reminiscence processes. As well as, it may assist to raised perceive issues related to an impaired capacity to hyperlink recollections.
“Our findings are important for understanding how memories are linked across time to form memory episodes as well as for addressing memory deficits whereby memory linking is impaired, such as those linked to Alzheimer’s disease,” defined Poirazi.
“By providing a mechanistic understanding of memory linking, our work serves as a first step towards the development of new treatments that may target such mechanisms in order to remedy respective memory deficits.”
Of their future analysis, Sehgal and her lab at The Ohio State College will proceed exploring the underpinnings of dendritic plasticity that contributes to the linking and encoding of recollections. As well as, they plan to additional examine the memory-related plasticity patterns that they noticed as a part of their latest examine.
“We discovered that compartmentalized plasticity plays a critical role in dictating how memories are stored in the future, but we do not know the underlying mechanisms,” stated Sehgal. “My lab is now digging deeper into the circuit and molecular processes that allow this plasticity.”
Poirazi and her collaborators on the Basis for Analysis and Expertise at the moment are working to increase their computational fashions to simulate different mind areas and their contribution to completely different cognitive duties. They hope that these fashions will assist them to raised perceive the position of dendritic mechanisms in studying and reminiscence features, whereas additionally unveiling a few of their most necessary options.
“In parallel, given the key role of dendrites in biological learning and memory, we initiated a new research line whereby we adopt dendritic mechanisms in artificial neural network systems (e.g., Chavlis and Poirazi, Nature Communications 2025), with the aim of making machine learning and artificial intelligence systems more robust, intelligent and efficient, like the brain.”
Extra info:
Megha Sehgal et al, Compartmentalized dendritic plasticity within the mouse retrosplenial cortex hyperlinks contextual recollections shaped shut in time, Nature Neuroscience (2025). DOI: 10.1038/s41593-025-01876-8
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