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Our biceps and our mind cells could have extra in widespread than beforehand thought.
New analysis led by the Lippincott-Schwartz Lab reveals {that a} community of subcellular constructions just like these liable for propagating molecular indicators that make muscle mass contract are additionally liable for transmitting indicators within the mind that will facilitate studying and reminiscence.
“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 Chief Jennifer Lippincott-Schwartz. “The same machinery is operating in both cases but with different readouts.”
The primary clue in regards to the attainable connection between mind and muscle cells got here when Janelia scientists seen one thing unusual in regards to the endoplasmic reticulum, or ER—the membranous sheets and folds inside cells which can be essential for a lot of mobile features.
Lorena Benedetti, a analysis scientist within the Lippincott-Schwartz Lab, was monitoring molecules at excessive decision alongside the floor of the ER in mammalian neurons when she noticed that the molecules have been tracing a repeating, ladder-like sample alongside your entire size of the dendrites—the branch-like extensions on mind cells that obtain incoming indicators.
Across the similar time, Senior Group Chief Stephan Saalfeld alerted Lippincott-Schwartz to high-resolution 3D electron microscopy photos of neurons within the fly mind the place the ER was additionally forming recurrently spaced, transversal constructions.
The ER usually seems like an enormous, dynamic web, in order quickly as Lippincott-Schwartz noticed the constructions, she knew her lab wanted to determine what they have been for.
“In science, structure is function,” says Lippincott-Schwartz, who additionally heads Janelia’s 4D Mobile Physiology analysis space. “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, began by trying on the solely different space of the physique recognized to have related, ladder-like ER constructions: muscle tissue. In muscle cells, the ER and the plasma membrane—the outer membrane of the cell—meet at periodic contact websites, an association managed by a molecule referred to as junctophilin.
New analysis particulars the subcellular constructions in neurons that allow indicators to be transmitted from the place they’re obtained at particular websites on dendrites to the decision-making cell physique situated lots of of micrometers away. The brand new analysis finds that the endoplasmic reticulum and the plasma membrane kind contact websites the place specialised molecules management the discharge of calcium, which regulates the indicators despatched alongside the dendrite to the soma. This film reveals 3D renderings of those constructions in high-resolution 3D electron microscopy photos of fruit fly neurons. The endoplasmic reticulum (inexperienced), plasma membrane (blue), mitochondria (pink), microtubules (tan), and ER-plasma membrane contacts (magenta) are segmented from FIB-SEM datasets of a Drosophila melanogaster MBON1 neuron. Credit score: Benedetti et al.
Utilizing high-resolution imaging, the researchers found that dendrites additionally include a type of junctophilin that controls contact websites between their ER and plasma membrane. Additional, the crew discovered that the identical molecular equipment controlling calcium launch at muscle cells’ contact websites—the place calcium drives muscle contraction—was additionally current at dendrite contact websites—the place calcium regulates neuronal signaling.
Due to these clues, the researchers had a hunch that the molecular equipment on the dendritic contact websites should even be vital for transmitting calcium indicators, which cells use to speak. They suspected that the contact websites alongside the dendrites would possibly act like a repeater on a telegraph machine: receiving, amplifying, and propagating indicators over lengthy distances. In neurons, this might clarify how indicators obtained at particular websites on dendrites are relayed to the cell physique lots of of micrometers away.
“How that information travels over long distances and how the calcium signal gets specifically amplified was not known,” says 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.”
The researchers discovered that this course of is triggered when a neuronal sign causes calcium to enter the dendrite by way of voltage-gated ion channel proteins, that are positioned on the contact websites. Though this preliminary calcium sign dissipates shortly, it triggers the discharge of extra calcium from the ER on the contact web site.
This inflow of calcium on the contact web site attracts and prompts a kinase referred to as CaMKII, a protein recognized to be vital in reminiscence. CaMKII alters the plasma membrane’s biochemical properties, altering the power of the sign that’s handed down the plasma membrane.
This course of continues from contact web site to contact web site all alongside the dendrite to the cell physique, the place the neuron decides the way it will talk with different neurons.
The brand new analysis reveals a novel mechanism for sign transmission in mind cells and helps reply an open query in neuroscience about how intracellular indicators journey over lengthy distances in neurons, enabling info obtained at particular websites on dendrites to be processed within the mind.
It additionally sheds gentle on the molecular mechanisms underlying synaptic plasticity—the strengthening or weakening of neuronal connections that permits studying and reminiscence. Determining this course of on the molecular stage might enhance understanding of how the mind works usually and in ailments the place 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.”
Extra info:
Lorena Benedetti et al, Periodic ER-plasma membrane junctions assist long-range Ca2+ sign integration in dendrites, Cell (2024). DOI: 10.1016/j.cell.2024.11.029
Journal info:
Cell
Supplied by
Howard Hughes Medical Institute
Quotation:
Mind cells mimic muscle signaling to reinforce studying and reminiscence (2025, February 8)
retrieved 8 February 2025
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