Brain Cells Use Muscle-Like Signals to Strengthen Learning and Memory

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https://neurosciencenews.com/dendrite-memory-learning-muscle-28406/

February 7, 2025

This mechanism explains how neurons process information received at specific points and relay it to the cell body. Understanding this process sheds light on synaptic plasticity, which underlies learning and memory formation. The findings could provide new insights into neurodegenerative diseases like Alzheimer’s.

Key Facts:

● Neural Calcium Amplification: Brain cells use structured ER contact sites to amplify calcium signals, similar to how muscle cells trigger contractions.

● Memory and Learning Connection: These calcium signals activate CaMKII, a protein critical for strengthening neuronal connections and memory formation.

● Potential Disease Insights: Understanding this mechanism could help explain cognitive dysfunction in conditions like Alzheimer’s disease.

Our biceps and our brain cells may have more in common than previously thought.

New research led by the Lippincott-Schwartz Lab shows that a network of subcellular structures similar to those responsible for propagating molecular signals that make muscles contract are also responsible for transmitting signals in the brain that may facilitate learning and memory.

“Einstein said that when he uses his brain, it is like he is using a muscle, and in that respect, there is some parallel here,” says Janelia Senior Group Leader Jennifer Lippincott-Schwartz.

Around the same time, Senior Group Leader Stephan Saalfeld alerted Lippincott-Schwartz to high-resolution 3D electron microscopy images of neurons in the fly brain where the ER was also forming regularly spaced, transversal structures.

The ER normally appears like a huge, dynamic net, so as soon as Lippincott-Schwartz saw the structures, she knew her lab needed to figure out what they were for.

“In science, structure is function,” says Lippincott-Schwartz, who also heads Janelia’s 4D Cellular Physiology research area.

“This is an unusual, beautiful structure that we are seeing throughout the whole dendrite, so we just had this feeling that it must have some important function.”

The researchers, led by Benedetti, started by looking at the only other area of the body known to have similar, ladder-like ER structures: muscle tissue.

In muscle cells, the ER and the plasma membrane – the outer membrane of the cell – meet at periodic contact sites, an arrangement controlled by a molecule called junctophilin.

Using high-resolution imaging, the researchers discovered that dendrites also contain a form of junctophilin that controls contact sites between their ER and plasma membrane.

Further, the team found that the same molecular machinery controlling calcium release at muscle cells’ contact sites — where calcium drives muscle contraction — was also present at dendrite contact sites — where calcium regulates neuronal signaling.

Because of these clues, the researchers had a hunch that the molecular machinery at the dendritic contact sites must also be important for transmitting calcium signals, which cells use to communicate.

The new research reveals a novel mechanism for signal transmission in brain cells and helps answer an open question in neuroscience about how intracellular signals travel over long distances in neurons, enabling information received at specific sites on dendrites to be processed in the brain.

It also sheds light on the molecular mechanisms underlying synaptic plasticity – the strengthening or weakening of neuronal connections that enables learning and memory.

Image: Figuring out this process at the molecular level could increase understanding of how the brain works normally and in diseases where these processes go awry, like Alzheimer’s.

“We are showing that a structure – a beautiful structure – operating at a level of subcellular organization is having a huge effect on the way the entire neuronal system is operating vis-à-vis calcium signaling,” Lippincott-Schwartz says.

“This is a great example of how, in doing science, if you see a beautiful structure, it can take you into a whole new world.”

This process continues from contact site to contact site all along the dendrite to the cell body, where the neuron decides how it will communicate with other neurons.

The new research reveals a novel mechanism for signal transmission in brain cells and helps answer an open question in neuroscience about how intracellular signals travel over long distances in neurons, enabling information received at specific sites on dendrites to be processed in the brain.

It also sheds light on the molecular mechanisms underlying synaptic plasticity – the strengthening or weakening of neuronal connections that enables learning and memory.