Neuroscience

Salk faculty Joseph Ecker, Margarita Behrens and colleagues analyzed over 100,000 mouse brain cells using a scientific technique that identifies a chemical pattern called methylation, which is one way cells control gene expression. The scientists then applied this technique to thousands of cells from 45 different regions of the mouse brain and identified 161 clusters of cell types, each distinguished by its pattern of methylation. The team also showed that the methylation patterns could be used to predict where in the brain any given cell came from—not just within broad regions but down to specific layers of cells within a region. This means that eventually drugs could be developed that act only on small groups of cells by targeting their unique epigenomics.

Professors Ecker, Callaway and colleagues studied the association between DNA methylation and neural connections. The team developed a new way of isolating cells that connect regions of the brain and used the approach on over 11,000 individual mouse neurons, all extending outward from the mouse cortex. The patterns of methylation in the cells, they discovered, correlated with cells’ destination patterns.

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As you read this article, touch receptors in your skin are sensing your environment. But, unless a stimulus is particularly unexpected or required to help you orient your own movements, your brain ignores many of these inputs. Now, Assistant Professor Eiman Azim, first author and Staff Researcher James Conner and colleagues have discovered how neurons in a small area of the mammalian brain help filter distracting or disruptive signals—specifically from the hands—to coordinate dexterous movements. Their results may hold lessons in how the brain filters other sensory information as well.

It’s long been known that opioid overdose deaths are caused by disrupted breathing, but the actual mechanism by which these drugs suppress respiration was not understood. Now, a new study by Assistant Professor Sung Han, first author Shijia Liu and colleagues identified a group of neurons in the brainstem that plays a key role in this process. The findings show how triggering specific receptors in these neurons causes opioid-induced respiratory depression, or OIRD, the disrupted breathing that causes overdose deaths. It also shows how blocking these receptors can cause OIRD to be reversed.