Shutting off neurons helps bullied mice overcome symptoms of depression

August 29, 2013

A new drug target to treat depression and other mood disorders may lie in a group of GABA neurons (gamma-aminobutyric acid –the neurotransmitters which inhibit other cells) shown to contribute to symptoms like social withdrawal and increased anxiety, Penn Medicine researchers report in a new study in the Journal of Neuroscience.

Experts know that people suffering from depression and other mood disorders often react to rejection or bullying by withdrawing themselves socially more than the average person who takes it in strides, yet the biological processes behind these responses have remained unclear.

Now, a preclinical study, from the lab of Olivier Berton, PhD, an assistant professor in the department of Psychiatry, in collaboration with Sheryl Beck, PhD, a professor in the department of Anesthesiology at Children's Hospital of Philadelphia, found that bullying and other social stresses triggered in mice by activating GABA neurons, in a never-before-seen direct relationship between social stimuli and this . Activation of those neurons, they found, directly inhibited levels of serotonin, long known to play a vital role in —without it, a depressed person is more likely to socially withdrawal.

Conversely, when the researchers successfully put the brake on the GABA neurons, mice became more resilient to bullying and didn't avoid once -perceived threats.

"This is the first time that GABA —found deep in the —has been shown to play a key role in the associated with social approach or in mammals," said Dr. Berton. "The results help us to understand why current antidepressants may not work for everyone and how to make them work better—by targeting GABA neurons that put the brake on serotonin cells."

Less serotonin elicits socially defensive responses such as avoidance or submission, where enhancement—the main goal of antidepressants—induces a positive shift in the perception of socio-affective stimuli, promoting affiliation and dominance. However, current antidepressants targeting serotonin, like SSRIs, are only effective in about 50 percent of patients.

These new findings point to GABA neurons as a new, neural that could help treat the other patients who don't respond to today's treatment.

For the study, "avoidant" mice were exposed to brief bouts of aggression from trained "bully" mice. By comparing gene expression in the brains of resilient and avoidant mice, Berton and colleagues discovered that bullying in avoidant mice puts GABA neurons in a state where they become more excitable and the mice exhibit signs of social defeat. Resilient mice, however, had no change in neuron levels and behavior.

To better understand the link between GABA and the development of stress resilience, Berton, Beck, and colleagues also devised an optogenetics-based approach to directly manipulate levels: Lifting GABA inhibition of serotonin neurons reduced social and anxiety symptoms in mice exposed to bullies and also fully prevented neurobiological changes due to stress.

"Our paper provides a novel cellular understanding of how social defensiveness and develop in mice and gives us a stepping stone to better understand the basis of similar social symptoms in humans," said Berton. "This has important implications for the understanding and treatment of mood disorders."

Explore further: Gatekeeper of brain steroid signals boosts emotional resilience to stress

Related Stories

Gatekeeper of brain steroid signals boosts emotional resilience to stress

April 23, 2012
A cellular protein called HDAC6, newly characterized as a gatekeeper of steroid biology in the brain, may provide a novel target for treating and preventing stress-linked disorders, such as depression and post-traumatic stress ...

Putting the brakes on pain

August 5, 2013
Neuropathic pain—pain that results from a malfunction in the nervous system—is a daily reality for millions of Americans. Unlike normal pain, it doesn't go away after the stimulus that provoked it ends, and it also behaves ...

Exercise reorganizes the brain to be more resilient to stress

July 3, 2013
Physical activity reorganizes the brain so that its response to stress is reduced and anxiety is less likely to interfere with normal brain function, according to a research team based at Princeton University.

Neuron loss in schizophrenia and depression could be prevented

March 13, 2013
Gamma-aminobutyric acid (GABA) deficits have been implicated in schizophrenia and depression. In schizophrenia, deficits have been particularly well-described for a subtype of GABA neuron, the parvalbumin fast-spiking interneurons. ...

Brain's stem cells 'eavesdrop' to find out when to act

August 6, 2012
Working with mice, Johns Hopkins researchers say they have figured out how stem cells found in a part of the brain responsible for learning, memory and mood regulation decide to remain dormant or create new brain cells. Apparently, ...

Researchers find caffeine during pregnancy negatively impacts mice brains

August 8, 2013
(Medical Xpress)—A team of European researchers has found that mice who consume caffeine while pregnant give birth to pups with negative changes to their brains. In their paper published in the journal Science Translational ...

Recommended for you

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Speech language therapy delivered through the Internet leads to similar improvements as in-person treatment

July 20, 2017
Telerehabilitation helps healthcare professionals reach more patients in need, but some worry it doesn't offer the same quality of care as in-person treatment. This isn't the case, according to recent research by Baycrest.

New study reveals contrasts in how groups of neurons function during decision making

July 19, 2017
By training mice to perform a sound identification task in a virtual reality maze, researchers at Harvard Medical School and the Istituto Italiano di Tecnologia (IIT) have identified striking contrasts in how groups of neurons ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

cmn
5 / 5 (2) Aug 29, 2013
This is an interesting read, because GABA is an anxiety reducing drug. I guess it's a trade-off?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.