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

Cold Spring Harbor, NY -- A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL), Brookhaven National Laboratory (BNL) and UC San Diego (UCSD) has collected evidence suggesting that a previously overlooked portion of the brain could be a prime locus of human depression.

In two rat models of human depression, the scientists have demonstrated that neurons in a tiny area in the central brain called the lateral habenula (LHb) are hyperactive.

Specifically, as the team reports today online ahead of print in the journal Nature, excitatory synaptic inputs onto neurons in the LHb are enhanced in "depressed" animals, a finding they regard significant because this excitation in turn causes the inhibition of "downstream targets" -- including neurons in a part of the brain called the ventral tegmental area (VTA), important in the brain's reward system and heavily populated by dopamine neurons.

Furthermore, the team, which includes Professor Fritz Henn of CSHL and BNL and Assistant Professor Bo Li of CSHL, as well as Professor Roberto Malinow of UCSD, was able to use an analog of deep brain stimulation (DBS), a novel form of electrical stimulation involving the implantation of electrodes into a specific brain area, to reverse depression-like symptoms in the rats.

DBS is an important new experimental modality of treatment for refractory depression in people, as well as a potentially important approach to treat other neurophysiological disorders, most notably Parkinson's disease. The team's results point to the LHb as a potential therapeutic target for DBS. A series of ongoing experiments in depression at other laboratories, which have shown promise in a small number of human patients, have used DBS to target an area of the cingulate cortex called Brodman's Area 25. Henn and colleagues in Germany last year reported success in treating one case of intractable human depression with DBS, targeting the LHb.

The animal 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 activity," Henn states. Another priority, he says, is to better understand the mechanism of DBS in the habenula. "By applying DBS in the habenula, you're affecting the entire structure, and its entire population of neurons. We want to know which elements are critical in mediating the behavioral effect -- the relief of "depressed" symptoms -- that we have observed," Henn says.

The habenula projects not only to the VTA, but to other areas such as the Raphe nuclei, which produce serotonin, another neurotransmitter implicated in depression and which may control noradrenaline output in the brain as well. The team wants to know how the lateral habenula coordinates the activity of all three -- dopamine, serotonin and noradrenaline -- to fully understand the LHb's role in depression. Li says he intends to use highly specific methods including optogenetics to dissect different pathways of interest in the model.


'/>"/>

Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

Related medicine news :

1. Neuroscientists reveal new links that regulate brain electrical activity
2. Ion channel responsible for pain identified by UB neuroscientists
3. MIT neuroscientists explain Proustian effect of small details attached to big memories
4. Chlamydia Often Overlooked in Young Men
5. Depression overlooked in patients with hepatitis C; compromising HCV therapy
6. Some kids with spinal cord injury may be overlooked for walking rehabilitation
7. Damage of False-Positive Mammograms Overlooked: Study
8. Gadgets not related to teenagers brain pain
9. Dementia Rates Escalate as Brain Capacity Diminishes with Age
10. Researchers discover new way to kill pediatric brain tumors
11. Scientists Pinpoint Area of Brain That Fears Losing Money
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... ... "With 30 hand-drawn hand gesture animations, FCPX users can easily customize each ... Film Studios. , ProHand Cartoon’s package transforms over 1,300 hand-drawn pictures into hand ... select a ProHand generator and drag it above media or text in the Final ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van Mitchell, Secretary ... Work award to iHire in recognition of their exemplary accomplishments in worksite health promotion. ... Maryland Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... June 19, ... the dangers associated with chronic pain and the benefits of holistic treatments, Serenity ... who are suffering with Sickle Cell Disease. , Sickle Cell Disease (SCD) is a ...
(Date:6/24/2016)... ... June 24, 2016 , ... Dr. Amanda ... orthodontic treatment. Dr. Cheng has extensive experience with all areas of orthodontics, including ... accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary adjunct to orthodontic treatment. ...
(Date:6/24/2016)... Norcross, Georgia (PRWEB) , ... June 24, 2016 ... ... Year” awards today at the Clinical Decision Making in Emergency Medicine conference in ... who have authored journal articles published in Emergency Medicine Practice and ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016 Roche (SIX: RO, ROG; ... for its Elecsys BRAHMS PCT (procalcitonin) assay as a ... septic shock. With this clearance, Roche is the first ... integrated solution for sepsis risk assessment and management. ... infection and PCT levels in blood can aid clinicians ...
(Date:6/23/2016)... 23, 2016 Research and Markets has ... 52" report to their offering. ... creates a favourable commercial environment for MedImmune to enter. The ... that will serve to drive considerable growth for effective anti-influenza ... to cap sales considerably, but development is still in its ...
(Date:6/23/2016)... INDIANAPOLIS , June 23, 2016 If ... Leaders Scholarship is any indication, the future is in ... at www.diabetesscholars.org by the Diabetes Scholars Foundation ... the way of academic and community service excellence. ... since 2012, and continues to advocate for people with ...
Breaking Medicine Technology: