A new imaging tool created by the National Institutes of Health (NIH)-led Brain Research through Advancing Innovative Neurotechnologies (BRAIN) makes it possible to capture images of more protein targets faster than traditional methods.
The imaging tool allows researchers to view dozens of proteins in a single tissue sample with thousands of neural connections.
The tool produces a rainbow of images, each one capturing different proteins with the complex network of synapses. The proteins could be present in different amounts and locations in a network.
“Such findings may shed light on key differences among synapses, as well as provide new clues into the roles that synaptic proteins may play in schizophrenia and various other neurological disorders,” wrote Francis Collins, M.D., Ph.D., director of NIH.
Researchers at Massachusetts Institute of Technology and Harvard University adapted an existing imaging method called DNA PAINT to better observe working synaptic proteins — something that has often presented many obstacles for researchers.
The adapted method is called PRISM (Probe-based Imaging for Sequential Multiplexing).
Researchers labeled proteins and molecules using antibodies that recognize the proteins. The antibodies include a DNA probe to help make the proteins visible through a microscope.
In DNA PAINT, strands of DNA bind and unbind to create a blinking fluorescence captured using super-resolution microscopy. This method, researchers said, is very slow.
To overcome this, the research team altered the DNA probes using synthetic DNA designed to bind more tightly to the antibody.
PRISM helped researchers go through the imaging process more quickly, though the resolution is slightly lower. While the research team currently captures 12 proteins in a sample in about an hour, it is possible the number could increase to 30, the researchers reported in the journal Nature Communications.
“PRISM will help (researchers) learn more mechanistically about the inner workings of synapses and how they contribute to a range of neurological conditions,” Collins wrote.