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Study of Brain Circuits Finds Links To Depression Symptoms

UC San Diego

Byungkook Lim (left), associate professor of neurobiology, and Daniel Knowland, neurobiology graduate student, in Lim’s laboratory at UC San Diego.

Scientists at UC San Diego announced Monday that they linked specific wiring in the brain to behavioral symptoms of depression.

In a study published in the journal Cell, researchers in the school's Division of Biological Sciences found brain circuits that are tied to feelings of despair and helplessness, and were able to alleviate and even reverse such symptoms in mice studies.

"We took an approach of studying depression in the sense that different brain areas and circuits of the brain might mediate or contribute to very discrete aspects of depression,'' said Daniel Knowland, a UCSD graduate student and first author of the study. "For example, brain area A might contribute to loss of appetite, brain area B to social withdrawal and so forth.''

The researchers tracked brain pathways and specific areas of neurons via imaging and behavioral models. Two populations of neurons were identified in the brain's ventral pallidum region — part of the basal ganglia, which is connected to multiple brain areas — as key to depressive behavior.

They found that specifically modifying pathways in the two areas in a mouse displaying depression led to improved behavioral changes similar to those of a healthy mouse.

The scientists were also able to examine connections across multiple regions and how one impacted the other, where previous studies had mainly focused on the role of certain brain areas in isolation.

Senior author Byungkook Lim, an assistant professor in the Neurobiology Section, said the results require more study before they can be applied to humans with depression. However, the study in animal models provides solid grounding, he said.

"This is one of the first studies providing clear evidence showing that different brain circuitry is involved in different types of depressive behavior with specific symptoms,'' Lim said. "Each area of the brain is different with distinct cell types and connectivity, so if we can confirm that one area of circuitry is more involved in a particular symptom than another, we may eventually be able to treat a depression patient more efficiently than treating everyone the same way.''

The study was financially backed by a pair of grants from the National Institutes of Health, with added support from the Klingenstein Fund of New York, Searle scholar program of Chicago and the Whitehall Foundation of Palm Beach, Florida.

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