Researchers uncover brain circuitry central to reward-seeking behavior

February 22, 2017
Green: NAc-projecting prefrontal cortex neurons become active during the presentation of a reward-predictive cue, and this activity drives reward-seeking behavior. Purple: PVT-projecting prefrontal cortex neurons inhibited during reward-predictive cue. Credit: The Stuber Lab (UNC School of Medicine)

The prefrontal cortex, a large and recently evolved structure that wraps the front of the brain, has powerful "executive" control over behavior, particularly in humans. The details of how it exerts that control have been elusive, but UNC School of Medicine scientists, publishing today in Nature, have now uncovered some of those details, using sophisticated techniques for recording and controlling the activity of neurons in live mice.

The UNC scientists, led by Garret Stuber, PhD, associate professor in UNC's departments of psychiatry and cell biology & physiology, examined two distinct populations of prefrontal neurons, each of which project to a different region outside the cortex. The researchers found that as mice learn to associate a particular sound with a rewarding sugary drink, one set of prefrontal neurons becomes more active and promotes what researchers call reward-seeking behavior - a sign of greater motivation. By contrast, other prefrontal neurons are silenced in response to the tone, and those neurons act like a brake on reward-seeking.

"We've known that there are a lot of differences in how prefrontal neurons respond to stimuli, but nobody has really been able to map these differences onto the intrinsic wiring of the brain," said Stuber, senior author of the study and member of the UNC Neuroscience Center.

Stuber and colleagues obtained their findings with the use of three sophisticated and relatively new neuroscience tools: deep-brain two-photon imaging, optogenetics, and genetic techniques for labeling neurons by their projection targets in the brain. The successful combination of these tools heralds their future common use in defining the pathways and functions of many other brain networks to help uncover the roots of both normal and abnormal behavior.

The study, conducted by first authors and UNC postdoctoral fellows James Otis, PhD, and Vijay Namboodiri, PhD, focused on the dorsomedial (upper-middle) , or dmPFC.

"This region is critical for reward processing, decision making, and cognitive flexibility among other things, but how distinct populations of neurons within dmPFC orchestrate such phenomena were unclear," Stuber said.

Stuber and colleagues examined how the activity of dmPFC neurons changes during a Pavlovian reward-conditioning process. In this process, mice learn to associate an auditory tone with a taste of sugary liquid until the tone itself is enough to make the animals start licking around their mouths in anticipation.

"This simple experiment models a learning phenomenon that occurs in lots of different ," Stuber said. "It is critical for motivation and decision making, and of course it can go awry in drug and food addiction, depression, and other neuropsychiatric disorders."

As the mice in the experiment learned to associate the tone with the sweet drink, the researchers found that a subset of the mouse dmPFC neurons became increasingly excited when the tone sounded, whereas another subset went increasingly silent. The researchers were able to observe this phenomenon by using a deep-brain version of two-photon imaging, a technique in which a microscope visualizes hundreds of brain cells simultaneously in mice that are awake and able to perform some ordinary behaviors.

The dmPFC is known to output many of its chemical signals to two other brain regions, the nucleus accumbens (NAc) and the paraventricular nucleus of the thalamus (PVT), both of which are considered important for reward-directed behavior. Stuber's team found that the NAc-projecting neurons in the dmPFC were the ones that became increasingly excited by the tone, and the PVT-projecting neurons were the ones that became increasingly suppressed. The two sets of neurons turned out to be physically separate within the dmPFC only by a few hundred micrometers.

The team then used optogenetic techniques to artificially drive the activities of these neurons. Optogenetics allows researchers to use beams of light to activate specific populations of neurons. Driving the NAc-projecting neurons caused the mice to anticipate their sweet reward more intensely, with more licks after the tone. By contrast, driving the PVT-projecting neurons muted that anticipatory, reward-seeking behavior.

The findings represent a basic demonstration of how the dmPFC has evolved anatomically distinct neuronal populations that have functionally distinct control over behavior, Stuber said. And the discovery points to the existence of similar combinations of control mechanisms elsewhere in the brain.

He and his colleagues are now following up with studies of dmPFC that project to other brain regions.

Explore further: Scientists illuminate the neurons of social attraction

More information: Prefrontal cortex output circuits guide reward seeking through divergent cue encoding, nature.com/articles/doi:10.1038/nature21376

Related Stories

Scientists illuminate the neurons of social attraction

January 30, 2017
The ancient impulse to procreate is necessary for survival and must be hardwired into our brains. Now scientists from the University of North Carolina School of Medicine have discovered an important clue about the neurons ...

New deep-brain imaging reveals separate functions for nearly identical neurons

January 29, 2015
Researchers at the UNC School of Medicine have used new deep-brain imaging techniques to link the activity of individual, genetically similar neurons to particular behaviors of mice. Specifically, for the first time ever ...

Research shows how two brain areas interact to trigger divergent emotional behaviors

March 20, 2013
New research from the University of North Carolina School of Medicine for the first time explains exactly how two brain regions interact to promote emotionally motivated behaviors associated with anxiety and reward.

Scientists take step toward mapping how the brain stores memories

January 3, 2017
A new study led by scientists at The Scripps Research Institute (TSRI) sheds light on how the brain stores memories. The research, published recently in the journal eLife, is the first to demonstrate that the same brain region ...

When neurons are 'born' impacts olfactory behavior in mice

December 7, 2016
New research from North Carolina State University shows that neurons generated at different life stages in mice can impact aspects of their olfactory sense and behavior. The work could have implications for our understanding ...

Positive and negative memories and behaviors are split up in the brains of mice

October 17, 2016
Like broccoli and ice cream on a toddler's plate, the brain also keeps nice and nasty information in separate places. Within the amygdala, an important memory center in the brain, pleasant experiences, tastes, and smells ...

Recommended for you

Firing of neurons changes the cells that insulate them

August 22, 2017
Through their pattern of firing, neurons influence the behavior of the cells that upon maturation will provide insulation of neuronal axons, according to a new study publishing 22 August in the open access journal PLOS Biology ...

Activating brain region creates intense desire to use cocaine

August 22, 2017
Researchers have identified a portion of the brain that intensifies one's desire for certain rewards—in this case, mimicking addiction to cocaine.

Study suggests serotonin may worsen tinnitus

August 22, 2017
Millions of people suffer from the constant sensation of ringing or buzzing in the ears known as tinnitus, creating constant irritation for some and severe anxiety for others. Research by scientists at OHSU shows why a common ...

Brain region mediates pleasure of eating

August 22, 2017
Providing the body with food is essential for survival. But even when full, we can still take pleasure in eating. Researchers at the Max Planck Institute of Neurobiology in Martinsried and the Friedrich Miescher Institute ...

Chronic stress induces fatal organ dysfunctions via a new neural circuit

August 22, 2017
Hokkaido University researchers revealed that fatal gut failure in a multiple sclerosis (MS) mouse model under chronic stress is caused by a newly discovered nerve pathway. The findings could provide a new therapeutic strategy ...

Contact in sports may lead to differences in the brains of young, healthy athletes

August 22, 2017
People who play contact sports show changes to their brain structure and function, with sports that have greater risk of body contact showing greater effects on the brain, a new study has found.

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.