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Stanford Researchers Find Brain Pathway of Depression in Rats

ded to develop a visualization tool that was faster and sharper than brain imaging systems currently available, such as MRI or CT scans.

Raag Airan, an MD/PhD student in Deisseroth's lab and co-first author of the study, led the development of a technique called voltage-sensitive dye imaging for this model. This technique allows intact brain circuits to be viewed in real time, enabling the researchers to watch living neurons in action, across entire brain networks.

The system uses a fluorescent dye, sensitive to brain circuit activity, which the researchers introduce into the animal brain tissue. As dyed circuits light up and darken again in response to electrical activity, very fast high-resolution cameras capture the action. The researchers can observe how different stimuli received by the animal, such as a dose of an antidepressant drug, affect circuit operation.

The researchers used slices of rat brain, Deisseroth said, "like a computer repair technician would take out a circuit board" to test its functional properties. The brain slices, which remain active for many hours, came from parts of the hippocampus, a region long implicated in depression. They also tested slices from rats treated with the antidepressant medications fluoxetine and imipramine.

The team carried out the study using a standard rat model of depression. Even though the rats do not mimic the entire complexity of genetic and environmental causes of human depression, Deisseroth explained, the animals exhibit similar symptoms and also get better from the same medications that work on humans.

In these rats, they found an alteration in electrical activity flow through the brain that could be corrected by human antidepressants. The extent that the signal spread through the brain sample was diminished in the "depressed" rats, a crucial finding that would not be apparent with other experimental methods, Deisseroth said. They needed to be able to image a whole circuit
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