Scientists debut START, a new tool for mapping the brain's intricate neuronal connections with unparalleled precision.
Scientists debut START, a new tool for mapping the brain's intricate neuronal connections with unparalleled precision. They demonstrate START's ability to identify the connectivity patterns of transcriptomic neuronal subtypes, and explain how the tool will help us design novel therapeutics that target certain neurons and circuits with greater specificity, efficacy, and fewer side effects.
It's like trying to repair a car without knowing what an engine or an axle is, he says. But if you had a diagram of the car's parts, you could start to understand how they might work together to make the wheels spin and the car move. That knowledge would then make it much easier to spot a problem in the system and figure out which tools you'll need to fix it.
To create START, the Callaway lab engineered a way to combine single-cell RNA sequencing with another technique they had developed previously: monosynaptic rabies virus tracing. The approach lets a modified virus hop from one cell type of interest to only the cells directly connected to it. By detecting where the virus ends up, the researchers can map which cells are connected to which.
For example, the researchers were able to resolve an inhibitory subtype called Sst Chodl cells, which are thought to be associated with sleep regulation. Using START, they found that Chodl cells were the cell type most densely connected to layer 6 excitatory neurons, which are known to project to the thalamus to coordinate sleep rhythms.
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