Salk scientists invent wearable microscopes to produce high-definition, real-time images of mouse spinal cord activity across previously inaccessible regions

The spinal cord acts as a messenger, carrying signals between the brain and body to regulate everything from breathing to movement.

While the spinal cord is known to play an essential role in relaying pain signals, technology has limited scientists’ understanding of how this process occurs on a cellular level.

Now, Salk Institute scientists have created wearable microscopes to enable unprecedented insight into the signalling patterns that occur within the spinal cords of mice.

This technological advancement will help researchers better understand the neural basis of sensations and movement in healthy and disease contexts, such as chronic pain, itch, amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).

Senior author Axel Nimmerjahn, associate professor and director of the Waitt Advanced Biophotonics Center, said: “These new wearable microscopes allow us to see nerve activity related to sensations and movement in regions and at speeds inaccessible by other high-resolution technology.

“Our wearable microscopes fundamentally change what is possible when studying the central nervous system.”

See also: First wearable device for vocal fatigue developed


Multicolour imaging


The wearable microscopes are approximately 7 and 14 millimetres wide (about the width of a little finger or the human spinal cord) and offer high-resolution, high-contrast, and multicolour imaging in real-time across previously inaccessible regions of the spinal cord.

The new technology can be combined with a microprism implant, which is a small reflective glass element placed near the tissue regions of interest.

Erin Carey, co-first author of one of the studies and researcher in Nimmerjahn’s lab, said: “The microprism increases the depth of imaging, so previously unreachable cells can be viewed for the first time.

“It also allows cells at various depths to be imaged simultaneously and with minimal tissue disturbance.”

Pavel Shekhtmeyster, a former postdoctoral fellow in Nimmerjahn’s lab and co-first author on both studies, added: “We’ve overcome field-of-view and depth barriers in the context of spinal cord research.

“Our wearable microscopes are light enough to be carried by mice and allow measurements previously thought impossible.”


Co-ordinated signals


With the novel microscopes, Nimmerjahn’s team began applying the technology to gather new information about the central nervous system.

In particular, they wanted to image astrocytes, star-shaped non-neuronal glial cells, in the spinal cord because the team’s earlier work suggested the cells’ unexpected involvement in pain processing.

The team found that squeezing the tails of mice activated the astrocytes, sending co-ordinated signals across spinal cord segments.

Prior to the invention of the new microscopes, it was impossible to know what astrocyte activity looked like – or what any cellular activity looked like across those spinal cord regions of moving animals.

Daniela Duarte, co-first author of one of the studies and a researcher in Nimmerjahn’s lab said: “Being able to visualise when and where pain signals occur and what cells participate in this process allows us to test and design therapeutic interventions.

“These new microscopes could revolutionise the study of pain.”

Nimmerjahn’s team has already begun investigating how neuronal and non-neuronal activity in the spinal cord is altered in different pain conditions and how various treatments control abnormal cell activity.

The two papers that make up this research are published in Nature Communications and Nature Biotechnology.

Image: Salk researchers developed two wearable microscopes to image cellular activity in previously inaccessible regions of the spinal cord of moving mice in real-time. © Salk Institute.