Wearable microscopes enable spinal cord imaging in mice

While the spinal cord is known to play an essential role in relaying pain signals between the brain and the body, technology has limited our understanding of how this process occurs on a cellular level. Scientists at the Salk Institute for Biological Studies have now created wearable microscopes to enable new insight into the signalling patterns that occur within the spinal cords of mice, which will help researchers to better understand the neural basis of sensations and movement in both healthy and disease contexts. Their work has been detailed in two papers, published in Nature Communications and Nature Biotechnology.

The wearable microscopes are approximately 7 and 14 mm wide and offer high-resolution, high-contrast and multicolour imaging in real time across previously inaccessible regions of the spinal cord. The technology can also be combined with a microprism implant, which is a small reflective glass element placed near the tissue regions of interest.

“The microprism increases the depth of imaging, so previously unreachable cells can be viewed for the first time,” said Erin Carey, who contributed to both studies. “It also allows cells at various depths to be imaged simultaneously and with minimal tissue disturbance.”

Pavel Shekhtmeyster, 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.”

The scientists have already used their microscopes 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 their earlier work suggested the cells’ unexpected involvement in pain processing.

The team found that squeezing the tails of mice activated the astrocytes, sending coordinated 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.

Neurons in the spinal cord (blue), including those that send signals about pain (green), captured using one of the new wearable microscopes. Image credit: Salk Institute.

Senior author Axel Nimmerjahn said the wearable microscopes “fundamentally change what is possible when studying the central nervous system”, enabling the scientists to see nerve activity related to sensations and movement in regions and at speeds inaccessible by other high-resolution technology. The 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.

“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,” concluded Daniela Duarte, who contributed to both studies. “These new microscopes could revolutionise the study of pain.”

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