A newly discovered brain connection can explain how early-life stress and adversity disrupt operation of the brain’s reward circuit, according to a study with mice.
Impaired function of this circuit is thought to underlie several major disorders, such as depression, substance abuse, and excessive risk-taking. The finding offers a new therapeutic target for treating mental illness.
In Nature Communications, researchers describe the cellular changes in the brain’s circuitry caused by exposure to adversity during childhood.
“We know that early-life stress impacts the brain, but until now, we didn’t know how,” says senior author Tallie Z. Baram, professor departments of anatomy & neurobiology, pediatrics, neurology, and physiology & biophysics at the University of California, Irvine.
“Our team focused on identifying potentially stress-sensitive brain pathways. We discovered a new pathway within the reward circuit that expresses a molecule called corticotropin-releasing hormone that controls our responses to stress. We found that adverse experiences cause this brain pathway to be overactive,” she says.
“These changes to the pathway disrupt reward behaviors, reducing pleasure and motivation for fun, food, and sex cues in mice. In humans, such behavioral changes, called ‘anhedonia,’ are associated with emotional disorders.
“Importantly, we discovered that when we silence this pathway using modern technology, we restore the brain’s normal reward behaviors.”
Researchers mapped all the CRH-expressing connections to the nucleus accumbens, a pleasure and motivation hub in the brain, and found a previously unknown projection arising from the basolateral amygdala. In addition to CRH, projection fibers co-expressed gama-aminobutyric acid.
They found that this new pathway, when stimulated, suppresses several types of reward behaviors in male mice.
The study involved two groups of male and female mice. One was exposed to adversity early in life by living for a week in cages with limited bedding and nesting material, and the other was reared in typical cages. As adults, the early adversity-experiencing male mice had little interest in sweet foods or sex cues compared to typically reared mice. In contrast, adversity-experiencing females craved rich, sweet food. Inhibiting the pathway restored normal reward behaviors in males, yet it had no effect in females.
“We believe that our findings provide breakthrough insights into the impact of early-life adversity on brain development and specifically on control of reward behaviors that underlie many emotional disorders,” Baram says.
“Our discovery of the previously unknown circuit function of the basolateral amygdala-nucleus accumbens brain pathway deepens our understanding of this complex mechanism and identifies a significant new therapeutic target. Future studies are needed to increase our understanding of the different and sex-specific effects of early-life adversity on behavior.”
The National Institute of Health, the Bren Foundation, the George E. Hewitt Foundation for Biomedical Research, and the British Society for Neuroendocrinology Project Support funded the work.
Source: UC Irvine
