Our biceps and our brain cells can have more in common than was previously thought.
New research led by the Lippinott-Schwartz laboratory shows that a network of subcellular structures similar to those responsible for spreading molecular signals that make muscles contract are also responsible for transmitting signals in the brain that can facilitate learning and memory.
“Einstein said that when he uses his brain, it is as if he were using a muscle, and in that sense, there is something parallel here,” says Janelia’s senior group, Jennifer Lippinott-Schwartz. “The same machinery is working in both cases but with different readings.”
The first clue about the possible connection between brain and muscle cells occurred when Janelia scientists noticed something strange about the endoplasmic reticulum, or ER, membrane sheets and folds inside the cells that are crucial for many cellular functions.
Lorena Benedetti, a research scientist at the Lippinott -Schwartz laboratory, was tracking the molecules at high resolution along the surface of the room -the extensions similar to the branch in the brain cells that receive incoming signals.
Almost at the same time, the leader of the senior group Stephan Saalfeld warned Lippincott-Schwartz to images of high-resolution 3D electronic microscopy of neurons in the flying brain where the ER was also forming regularly spaced transverse structures.
The emergency room usually seems like a huge and dynamic network, so as soon as Lippincott-Schwartz saw the structures, she knew that her laboratory needed to discover what they were.
“In science, the structure is function,” says Lippinott-Schwartz, who also directs the 4D Cellular Physiology Research Area of Janelia. “This is an unusual and beautiful structure that we are seeing throughout the dendrite, so we only had the feeling that it must have some important function.”
The researchers, led by Benedetti, began looking at the only other area of the body that is known that it has similar Er structures of staircase: muscle tissue. In muscle cells, ER and plasma membrane, the outer membrane of the cell, are found in periodic contact sites, a disposition controlled by a molecule called yuctophilin.
Using high -resolution images, researchers discovered that dendrites also contain a yuctophilin form that controls the contact sites between their ER and the plasma membrane. In addition, the team found that the same molecular machinery that controlled the release of calcium at the contact sites of muscle cells, where calcium drives muscle contraction, was also present at the depth sites of Dendrite, where calcium regulates the neuronal signaling
Due to these clues, researchers had the feeling that molecular machinery at dendritic contact sites should also be important to transmit calcium signals, which cells use to communicate. They suspected that the contact sites along the dendrites could act as a repeater in a telegraph machine: receive, amplify and spread signals at long distances. In neurons, this could explain how the signals received in specific sites in dendrites are transmitted to the cell body to hundreds of micrometers away.
“The way in which this information travels to long distances and how the calcium signal is not known specifically,” says Benedetti. “We think that ER could play that role, and that these distributed contact sites regularly are spatially and temporarily localized amplifiers: they can receive this calcium signal, amplify this calcium signal locally and transmit this remote calcium signal.”
The researchers found that this process is triggered when a neuronal signal causes calcium to enter the dendrite through voltage activated ion channel proteins, which are placed in the contact sites. Although this initial calcium signal dissipates rapidly, it triggers the release of additional calcium from the ER in the contact site.
This influx of calcium on the contact site attracts and activates a kinase called Camkii, a protein that is known to be important in memory. Camkii alters the biochemical properties of the plasma membrane, changing the resistance of the signal that is passed through the plasma membrane.
This process continues from the contact site to the contact site along the dendrite to the cell body, where the neuron decides how it will communicate with other neurons.
New research reveals a new mechanism for signal transmission in brain cells and helps answer an open question in neuroscience about how intracellular signals travel to long distances in neurons, allowing the information received in specific sites in dendrites It is processed in the brain.
It also sheds light on the molecular mechanisms underlying synaptic plasticity: the strengthening or weakening of neural connections that allow learning and memory. Discovering this process at the molecular level could increase the understanding of how the brain works normally and in diseases where these processes go wrong, such as Alzheimer’s.
“We are demonstrating that a structure, a beautiful structure, which works at a level of subcellular organization is having a great effect on the way in which the entire neuronal system is working in the face of calcium signage,” says Lippinott-Schwartz. “This is a great example of how, when doing science, if you see a beautiful structure, you can take it to a completely new world.”