People Say The Brain Is A “Muscle”. Turns Out, It’s Kind Of True

A new study led by the Lippincott-Schwartz Lab at the Howard Hughes Medical Institute’s Janelia Research Campus found that some of the important brain signaling that underpins learning and memory relies on a similar mechanism to the signals that tell our muscles to contract. 

Scientist Lorena Benedetti was studying molecules associated with the endoplasmic reticulum (ER), a large structure inside human cells with vital roles in protein synthesis – it’s been described as a “quality-control organelle for protein homeostasis.”

Benedetti noticed the peculiar pattern these molecules were forming, like a repeating ladder all along the length of dendrites – the tree-branch-like extensions that project out from nerve cells.

Meanwhile, colleague Stephan Saalfeld had spotted similar arrangements in high-resolution microscope images taken of the ER inside fly brains. The unfamiliarity of the patterns caught the attention of senior group leader Jennifer Lippincott-Schwartz.

“In science, structure is function,” she said in a statement. “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 only other place in the body where such patterns had been observed before was inside muscles, so that was where the team focused their investigation. 

In muscle cells, the ER forms regular contact points with the cell membrane thanks to the action of a set of proteins called junctophilins. It’s at these contact points that calcium can be released to drive muscle contraction. 

With some sleuthing, helped out by high-resolution imaging techniques, the team discovered that junctophilins were present in dendrites too, and were also facilitating regular contact points between the ER and outer membrane. They suspected that these points could help propagate information the sometimes hundreds of micrometers along the dendrite back to the cell body.

“How that information travels over long distances and how the calcium signal gets specifically amplified was not known,” said Benedetti. “We thought that ER could play that role, and that these regularly distributed contact sites are spatially and temporally localized amplifiers: they can receive this calcium signal, locally amplify this calcium signal, and relay this calcium signal over a distance.”

Nerve signals trigger the release of calcium from the ER, which in turn attracts and activates a protein called CaMKIII, known to play a role in memory. CaMKIII interacts with the membrane, altering the strength of the signal passing along it. From contact point to contact point, all along the membrane, the process continues, just like the amplifiers on long underwater telephone cables. 

“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,” Lippincott-Schwartz said. This new and improved understanding of the brain communications involved in learning and memory could help with research into conditions like dementia, as well as just increasing our appreciation of how the brain works at a fundamental level. 

It also reminds us that there’s sometimes some truth to be found in our old sayings, as Lippincott-Schwartz pointed out: “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.”

The study is published in the journal Cell.