Scientists have developed a new method to track changes in synaptic proteins across the entire brain, according to a study published in Nature Neuroscience.
The technique, called dye estimation of the lifetime of proteins in the brain, or DELTA, offers an unprecedented view of how synaptic plasticity, critical for learning and memory, unfolds, according to the authors.
Synaptic plasticity, the ability of neuronal connections to strengthen or weaken in response to experience, has long been suspected as the foundation of memory formation. However, scientists have struggled to pinpoint exactly where these changes occur and whether they are widespread or concentrated in specific regions. With DELTA, scientists can now monitor the turnover of synaptic proteins, offering valuable insights into the brain’s ability to learn and adapt.
“While it’s known that protein turnover — protein synthesis and protein degradation — at synapses plays a crucial role in these processes, existing analytical methods lacked the resolution to map and visualize these changes across the entire brain at the level of individual synapses,” said Yi-Zhi Wang, PhD, research assistant professor in the Ken and Ruth Davee Department of Neurology‘s Division of Behavioral Neurology, who was a co-author of the study.
In the study, scientists observed the brains of mice engaged in associative learning tasks. They found that associative learning increased the turnover of receptor GluA2, most prominently in the hippocampal area, which is long recognized for its role in memory processing.
“Beyond learning tasks, environmental enrichment, such as cages with running wheels, more bedding and housing for example, led to widespread increases in synaptic protein turnover across multiple brain regions, suggesting that experience broadly influences synaptic dynamics,” said Jeffrey Savas, PhD, associate professor of Neurology in the Division of Behavioral Neurology, who was also a co-author of the study.
The development of DELTA paves the way for future research into the molecular and circuit basis of learning, memory and other cognitive processes.
“These findings are significant as they provide a comprehensive map of how learning and environmental factors influence synaptic protein dynamics at a granular level, offering insights into the molecular underpinnings of learning and memory,” Wang said.
Now, Wang, Savas and their collaborators will utilize DELTA to investigate how synaptic protein turnover is altered in Alzheimer’s disease and autism spectrum disorders, aiming to understand these conditions better.
This research was funded by the Howard Hughes Medical Institute, the PGA Foundation, CZI Collaborative Pairs Pilot Project Awards, the National Institutes of Health Grant S10 OD032464 and European Research Council grant MolDynForSyn number 945700 Horizon 2020.
