An expanding molecular toolbox untangles neural circuits

From by Esther Landhuis

Scientists are developing ways to probe the activity, function and organization of neurons in real time with increasing precision.

Different genes in a mouse brain slice are imaged in different colours using the BARseq2 technique

The BARseq2 technique can identify snippets of messenger RNA (colours) and help researchers see which brain layers those snippets are in. Credit: Yu-Chi Sun et al./Nature Neurosci.

Life is full of nervous reactions — a head snaps towards a voice, leg muscles tense at the sound of a starting gun and thirsty mice scamper towards a squirt of water when trained to respond to a certain tone.

The mechanisms behind such reward-related behaviours are notoriously difficult to unpick. Nerve cells often snake through multiple brain areas, and their long axons and dense, tree-like dendrites can spark cellular conversations with thousands upon thousands of neighbours. Neural filaments can be exceptionally fine, and their positioning is crucial: disruptions in neural networks can lead to a range of neurological conditions. Yet, “If you want to label more than a few neurons at the same time and then trace where their axons go, it’s really difficult”, says Xiaoyin Chen, a neuroscientist at the Allen Institute for Brain Science in Seattle, Washington.

Still, researchers are slowly creating the tools to untangle that complexity, harnessing the power of sequencing, optogenetics and protein engineering to trace neuronal connections, record their activity, measure their inputs and outputs and map their networks.


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