Mouse brain with doctored neurons

A 3D reconstruction shows a slice of a mouse’s brain (purple), including neurons (pink) doctored with a new variety of light-sensitive protein. Credit: Junchol Park/Joshua Dudman

Neuroscience

When proteins stand on their heads for science

Bioengineered molecules promise to bolster optogenetics, a widely used approach for studying neurons.

Flipping light-sensitive proteins upside down in cell membranes has expanded the utility of a popular technique for studying the brain.

Optogenetics relies on light-sensitive proteins called channelrhodopsins, which can be embedded in the cell membranes of neurons in the brain. Shining light on these neurons stimulates them to fire.

Alla Karpova and Joshua Dudman at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia, and their colleagues sought to expand the range of channelrhodopsins available to researchers. The team altered two channelrhodopsins so that they would sit upside down in cellular membranes, relative to their typical orientation.

One alteration allows more potassium ions to pass through the cell membrane compared with the original protein; this design could be useful for studying potassium channels in neurons and other cells. The other alteration caused the protein to switch from activating neurons to inhibiting them, and was used to control behaviour in mice.