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Shining Light on Mouse Brains Provides Clues in Development, Neurological Disorders

Optogenetics Provides Insights Into Basis of Fear, Addiction

Alzheimer’s disease and schizophrenia have been associated with problems in cells that contain the protein parvalbumin. These cells constitute almost one-tenth of the brain’s cells, but not much is known about what they do. By stimulating mouse brains with lasers, researchers have made some startling findings.

The Washington University researchers found surprising changes in hemodynamics when parvalbumin-containing cells are stimulated. The technique used relies on specially bred mice whose brains can be stimulated with laser pulses.

Optogenetics––stimulating the brain with light signals––has greatly increased our understanding of how the brain works, including how it processes fear and why people become addicted to drugs.

According to the researchers, optogenetics has the advantage of being convenient, less invasive, and repeatable. It’s also more direct as it doesn’t require inserting probes into mouse brains.

The team bred mice with channelrhodopsin, a light-sensitive protein, stuck to parvalbumin-expressing neurons, and mice with channelrhodopsin on excitatory Thy1-expressing cells. Each mouse group had their brains stimulated with lasers and the scientists compared the results.

When most neurons are stimulated, the brain provides them with more blood and oxygen. Although this occurred with the Thy1 cells, the blood flow and volume findings revealed the opposite response when parvalbumin-expressing cells were stimulated. The researchers concluded that the cells are able to retreat and fine-tune the blood supply in areas where they are activated.

They measured the blood and oxygen levels by shining a separate laser system—laser speckle contrasting imaging—on the brain. When the mice whiskers were touched, the parvalbumin cells could reduce the nearby blood and oxygen when excited. By measuring different areas, the researchers discovered the cells could also help send messages to distant corners of the brain to change their hemodynamics.

Even although the hemodynamic activity could be an indirect cause of the parvalbumin-expressing neurons being stimulated, the scientists were surprised to see similar activity in the more distant areas of the brain.

The researchers hope that, eventually, their findings and techniques will improve understanding of the role of parvalbumin in neurovascular coupling and reveal how it influences brain development or the formation of neurological disorders.

Source: Optical Society of America, April 9, 2019

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