“Then you can ask: How does cell type A communicate with cell type B?” Chen envisions several possible uses for CRACK, including studying the neural function of species beyond mice and humans for which tailored neuroscience tools may not be available, or answering “any question that involves trying to marry molecular information with dynamics-functional information” on the behavior of neurons. “Now, if you have a tissue of a thousand neurons, you can actually start to label all eleven, twelve, thirteen, fourteen, fifteen different types of neurons that we know exist,” Chen says. Prior to CRACK, researchers could only monitor the neural activity of one cell type at a time, Chen explains, and there was no feasible way to connect that activity to the molecular workings going on inside those cells because obtaining each type of information required separate experiments. “There was a technology gap that required marrying molecular information with the functional information” from behavioral studies that his lab focuses on, Chen tells The Scientist. CRACK allows researchers to first observe the electrical firing of neurons in the brain of a live mouse during a behavioral task, and then track the expression of specific genes in slices of the animal’s brain, ultimately linking specific cells and their molecular activities to particular behaviors.

The new technique, called comprehensive readout of activity and cell type markers (CRACK), combines calcium imaging microscopy with a variation on a DNA labeling approach called hybridization chain reaction–fluorescence in situ hybridization (HCR-FISH) to label and track mRNA.

From neuron to brain ebook