Study shines light on brain mechanism that controls reward enjoyment

March 21, 2012
This image shows VTA dopamine neurons (in red) and VTA GABA fibers (in green). Credit: Stuber Lab, UNC-Chapel Hill.

What characterizes many people with depression, schizophrenia and some other mental illnesses is anhedonia: an inability to gain pleasure from normally pleasurable experiences.

Exactly why this happens is unclear. But new research led by at the University of North Carolina at Chapel Hill School of Medicine may have literally shined a light on the answer, one that could lead to the discovery of new mental health therapies. A report of the study appears March 22 in the journal Neuron.

The study used a combination of genetic engineering and to manipulate the wiring of a specific population of deep in a portion of a midbrain area that's known to promote to reward.

"For many years it's been known that dopamine in the ventral midbrain, the , or VTA, are involved in reward processing and motivation. For example, they're activated during exposure to drugs of abuse and to naturally rewarding experiences," said study lead author Garret D. Stuber, PhD, assistant professor in the departments of Psychiatry and Cell and , and the UNC Neuroscience Center.

"The major focus in our lab is to determine what other sorts of or genetically defined neural populations might be modulating the activity of those neurons, whether it's increasing or decreasing their activity," Stuber said. "In our study we found that activation of the nearby VTA GABAergic neurons directly inhibit the function of dopamine neurons, which is something that's never been shown before."

In the past, researchers have tried to get a glimpse into the inner workings of the brain using or drugs, but those techniques couldn't quickly and specifically change only one type of cell or one type of connection. But optogenetics, a technique that emerged about six years ago, can.

In this study, the scientists used a transgenic animal with a foreign gene that has been inserted into its genome to express a bacterial enzyme that can cause DNA recombination only in GABA neurons and not dopamine cells. Using a gene transfer method developed at UNC and with the animal anesthetized, the Stuber team transferred light-sensitive proteins called "opsins" – derived from algae or bacteria that need light to grow – into the VTA, targeting GABA cells. The presence of these foreign opsins in GABA neurons allows researchers to excite or inhibit them by pumping light from a laser into brain tissue.

The animals were then tested in different reward situations, simple tasks in which they were trained to associate a cue with a sugar water reward from a bottle or were given the opportunity to drink the reward by "free licking," where they could drink as much as they want.

Then, via optical fibers, the researchers shined laser beams onto the genetically manipulated GABA neurons, activating them for 5 seconds during the cue period followed by reward. And on another day, they activated the neurons during reward consumption, when the animals were actively engaged in drinking the sugar water.

"And what we saw when we activated the cells during the cue period, or reward anticipation, it didn't do anything to the behavioral response at all; they showed no difference compared to non-stimulated animals," Stuber explained.

"And when they were actively engaging with the sucrose, we did see we could disrupt their consumption when we activated those cells. They immediately disengaged from drinking, stopped drinking the sucrose solution. And when the stimulus stopped, they would then return back and continue to drink it again."

During the "free licking" sessions, optical stimulation of GABA neurons resulted in disruption of sucrose consumption. The animals stopped drinking.

Using sophisticated electrophysiology and cell chemistry measures, the study team could monitor the activity of the GABA and . They found a direct link between GABA activation and dopamine suppression.

"So basically, it appears that these GABA neurons located in the VTA are just microns away from dopamine and are negative regulators of dopamine function," Stuber proposes.

"When they become active, their basic job is to suppress dopamine release. A dysfunction in these GABA neurons might potentially underlie different aspects of neuropsychiatric illness, such as depression. Thus, we could think of them as a new physiological target for various aspects of neuropsychiatric diseases."

Explore further: Study shows how neurons interact, could lead to new treatment for addiction

Related Stories

Study shows how neurons interact, could lead to new treatment for addiction

January 18, 2012
Harvard scientists have developed the fullest picture yet of how neurons in the brain interact to reinforce behaviors ranging from learning to drug use, a finding that might open the door to possible breakthroughs in the ...

'Optogenetics' used to control reward-seeking behavior

June 29, 2011
Using a combination of genetic engineering and laser technology, researchers at the University of North Carolina at Chapel Hill have manipulated brain wiring responsible for reward-seeking behaviors, such as drug addiction. ...

Discovery of brain's natural resistance to drugs may offer clues to treating addition

March 8, 2012
A single injection of cocaine or methamphetamine in mice caused their brains to put the brakes on neurons that generate sensations of pleasure, and these cellular changes lasted for at least a week, according to research ...

Recommended for you

The neural codes for body movements

July 21, 2017
A small patch of neurons in the brain can encode the movements of many body parts, according to researchers in the laboratory of Caltech's Richard Andersen, James G. Boswell Professor of Neuroscience, Tianqiao and Chrissy ...

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 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 ...

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.

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.

0 comments

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.