A microscope about the size of a penny is giving scientists a new window into the everyday activity of cells within the spinal cord. The innovative technology revealed that astrocytes--cells in the nervous system that do not conduct electrical signals and were traditionally viewed as merely supportive--unexpectedly react to intense sensation.
The new miniaturized microscope and related imaging methods, described by Salk Institute scientists on April 28, 2016 in Nature Communications, offer unprecedented insight into nervous system function and could lead to novel pain treatments for spinal cord injuries, chronic itch and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS).
Salk Institute scientists show the surprising involvement of cells called astrocytes in spinal sensory processing. Here, astrocytes (genetically labeled in green) in a spinal cord (co-stained with glial fibrillary acidic protein, red, to visualize its outline) react to the activity of sensation with their own chemical signals.
Credit: Salk Institute
The spinal cord is crucial for sensing and responding to the world. Sometimes it even works independently from the brain, such as when your hand recoils from a hot stove before the sensation has fully registered. But it is unknown exactly how the cells within the spinal cord encode these and other feelings from the skin or internal organs.
In the new study, senior author Axel Nimmerjahn, an assistant professor in Salk's Waitt Advanced Biophotonics Center, and his team improved upon the miniaturized microscopes they first described back in 2008. The researchers' new version--which features numerous hardware and software improvements--enabled them to visualize changes in cellular activity in awake, roaming mice.
"For a long time, researchers have dreamed of being able to record cellular activity patterns in the spinal cord of an awake animal. On top of that, we can now do this in a freely behaving animal, which is very exciting," says first author Kohei Sekiguchi, a Salk researcher and PhD student at the University of California, San Diego.
Most of the Salk team's previous work focused on deploying microscopes to observe the brains of living animals. The spinal cord, by contrast, presented a bigger challenge for several reasons. For example, unlike the brain, multiple, independently moving vertebrae surround the spinal cord. The spinal cord is also closer to pulsating organs (heart and lungs), which can hinder stable views of the cells within. However, by developing new microscopy and procedural and computational approaches, the team was able to overcome these challenges and capture the action of living cells in real time and during vigorous movements.
In the new work, the group found that distinct stimuli--such as light touch or pressure--activate different subsets of spinal sensory neurons. They also found that certain features, like the intensity or duration of a given stimulus, are reflected in the activity of the neurons.
To the team's surprise, astrocytes, traditionally thought to be passive support cells, also respond to stimuli (albeit differently than the neurons). Though the astrocytes cannot send electrical signals like neurons can, they generated their own chemical signals in a coordinated way during intense stimuli.
Nimmerjahn is excited about this result because his group has a longstanding interest in understanding astrocytes and their roles in nervous system function and disease. These cells are increasingly appreciated as important players in how the nervous system develops and operates and could serve as promising new drug targets, he says.
"Not only can we now study normal sensory processing, but we can also look at disease contexts like spinal cord injury and how treatments actually affect the cells," says Nimmerjahn.
The team is now working to simultaneously record touch or pain-related activity in the brain and spinal cord using additional iterations of the miniaturized microscopes, which allow them to monitor and manipulate multiple cell types at even higher resolutions.
Other researchers on the paper include the Salk Institute's Pavel Shekhtmeyster, Katharina Merten, Alexander Arena, Daniela Cook, Elizabeth Hoffman and Alexander Ngo.
The work was supported by grants from the National Institutes of Health, the Rita Allen Foundation, Whitehall Foundation and Brain Research Foundation; funds from the Waitt Foundation, Hearst Foundations and the Richard Allan Barry Family Charitable Foundation; and research fellowships from the Nakajima Foundation, Mary K. Chapman Foundation, Jesse and Caryl Philips Foundation, the Rose Hills Foundation, Deutsche Forschungsgemeinschaft (DFG) and the Catharina Foundation.
About the Salk Institute for Biological Studies:
Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.
Salk Communications | EurekAlert!
Switch-in-a-cell electrifies life
18.12.2018 | Rice University
Plant biologists identify mechanism behind transition from insect to wind pollination
18.12.2018 | University of Toronto
Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.
Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
18.12.2018 | Materials Sciences
18.12.2018 | Physics and Astronomy
18.12.2018 | Physics and Astronomy