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Neuroscientists find overlooked brain area is an important locus of depression
Date:2/23/2011

models used in the team's rat experiments displayed a behavior called learned helplessness. The rats were stressed in ways that were unpredictable and inescapable; over time, they developed depression-like symptoms, notably a lack of motivation to evade unpleasant stress. "It's not a perfect model of human depression by any means," says Li, "but it is very valuable, for it does enable us to study the neural mechanisms of certain aspects of depression in people."

The team's most important decision was to study the lateral habenula. "This is an area of the brain that has often been overlooked, perhaps because of its size." Li noted, "It covers an area only about 1-2 mm across." So far only two brain imaging studies have implicated the LHb in depression because of the difficulty in resolving it using existing technologies such as PET and fMRI..

Dr. Henn, a pioneer in using learned helplessness to study depression, persuaded the team to focus on the LHb, a structure whose potential role in depression intrigued him because the LHb has elevated metabolic activity in the congenital learned helplessness model developed in his lab. The team hypothesizes that the therapeutic effect of DBS on hyperactivity in the LHb is due to the silencing effect of the high-frequency electrical pulses delivered by the implanted electrodes.

Further study of this and more broadly the mechanism behind LHb-related dysfunction is the team's most immediate priority. The rodent medial prefrontal cortex, the counterpart of Brodman's Area 25 in humans, which has already been demonstrated to be implicated in at least a subset of human depression, is one of several brain areas that send axonal projections to the habenula, Li notes. "In theory, it could be the source of the 'driving force' that makes neurons in the LHb overexcited."

"Our next important goal is to define the source of the overactivity, which appears to be due to increased glutamatergic activ
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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