“Being able to visualize 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 revolutionize the study of pain,” said Daniela Duarte, co-first author and a researcher at Salk, in the press release.

Testing the wearable microscopes on mice

The study authors claim that their wearable microscope can provide high-resolution and colored real-time images of hard-to-reach parts of the spinal cord that couldn’t be accessed previously. Measuring only seven and 14 millimeters in width, the microscopes come equipped with a microprism that enables them to capture high-quality images of spinal cord tissues and cells.

Erin Carey, the co-first author of the study, explained, "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."

The researchers used the tiny wearable microscopes in mice to look at star-shaped astrocytes, non-neuronal glial cells (cells that provide metabolic support to neurons) of the spinal cord. Until now, it was impossible to have an up-close look at astrocyte activity as they are located in an inaccessible region of the spinal cord. 

During their previous studies, the researchers found hints that astrocytes might be playing a role in processing pain. It was time to validate these findings. They equipped the mice with wearable microscopes and then squeezed their tails to validate the past findings. 

Thanks to the wearables, researchers could see astrocyte activity in mice's spinal cords for the first time — and that too in color, depth, and high resolution. They noticed that the pain from the tail squeezing activated the astrocytes. Moreover, since the microscope setup was lightweight, the mice also faced no problem carrying it.

Senior study author Axel Nimmerjahn 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.” He further added, “Our wearable microscopes fundamentally change what is possible when studying the central nervous system.”

The study is published in the journal Nature Communications.

Study abstract:

While the spinal cord is known to play critical roles in sensorimotor processing, including pain-related signaling, corresponding activity patterns in genetically defined cell types across spinal laminae have remained challenging to investigate. Calcium imaging has enabled cellular activity measurements in behaving rodents but is currently limited to superficial regions. Here, using chronically implanted microprisms, we imaged sensory and motor-evoked activity in regions and at speeds inaccessible by other high-resolution imaging techniques. To enable translaminar imaging in freely behaving animals through implanted microprisms, we additionally developed wearable microscopes with custom-compound microlenses. This system addresses multiple challenges of previous wearable microscopes, including their limited working distance, resolution, contrast, and achromatic range. Using this system, we show that dorsal horn astrocytes in behaving mice show sensorimotor program-dependent and lamina-specific calcium excitation. Additionally, we show that tachykinin precursor 1 (Tac1)-expressing neurons exhibit translaminar activity to acute mechanical pain but not locomotion.