Newly Discovered Brain Connection Affects Reward Behavior in Mice
• Research Highlight
People who experience adversity during childhood are often at greater risk of developing mental illnesses in adulthood. A recent study led by Matthew Birnie, Ph.D. , of the University of California, Irvine, and colleagues, sheds light on how negative early life experiences may impact how we act in response to rewards, which is often disrupted in people with mental illnesses. They identified a new connection between the amygdala and the nucleus accumbens in the brains of mice that is sensitive to early life adversity and affects how mice respond to rewards. Targeting this important connection may help researchers develop new ways to prevent and treat stress-related mental disorders.
Different regions of the brain work together to determine how we behave. The development of these brain regions and the connections between them are affected by many different things, including experiences in early life, such as stress and deprivation. To understand how early life adversity might affect reward behavior and the development of mental illnesses, Dr. Birnie and colleagues investigated brain connections in mice that play a role in creating reward behaviors and express a stress-sensitive molecule called corticotropin-releasing hormone (CRH). This molecule is impacted by early life adversity and other stressors.
The researchers found a new CRH-sensitive connection coming from the basolateral amygdala into the nucleus accumbens in the brains of mice. The basolateral amygdala is a brain area involved in learning the association between an experience (good or bad) and an outcome. The nucleus accumbens is a brain area involved in pleasure and motivation.
The researchers used light to determine how stimulating the connection would impact the nucleus accumbens. They found that stimulating this connection reduced activity in the nucleus accumbens. The connection was distinct from other well-documented connections between the amygdala and nucleus accumbens.
To determine whether this connection plays a role in reward-related behaviors, the researchers stimulated it in male and female mice using chemical (chemogenetic) and light-based (optogenetic) methods, which can turn off and on the action of nerve cells in the brain. Stimulating the amygdala-nucleus accumbens connection reduced reward-related behaviors in male but not female mice, suggesting this connection inhibits reward behavior—but only in male mice.
The reduced rewards-behavior seen in male mice when the connection was stimulated was similar to reward-behavior deficits seen in mice that had experienced early life stress. This finding suggested to the researchers that the connection may play a role in reward deficits related to experiences of early life adversity.
To test the role of this connection on reward-behavior deficits associated with early life adversity, the scientists blocked the connection between the amygdala and the nucleus accumbens in mice that had been exposed to early life stress. Blocking this connection in the mice restored their reward behavior, bringing it back in line with what is typically seen in mice who have not been exposed to early life stress. Blocking the connection had no effect on mice who had not been exposed to early life stress.
Together, the findings of this study provide evidence that the newly discovered connection between the basolateral amygdala and the nucleus accumbens is involved in reward-behavior deficits associated with early life adversity. Although this study was done in mice, the findings can inform our understanding of these processes in humans. More research is needed, but this discovery is a step toward understanding the mechanisms of stress-related mental disorders and developing new ways to prevent and treat them.
Birnie, M. T., Short, A. K., de Carvalho, G. B., Taniguchi, L., Gunn, B. G., Pham, A. L., Itoga, C. A., Xu, X., Chen, L. Y., Mahler, S. V., Chen, Y., & Baram, T. Z. (2023). Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice. Nature Communications, 14(1), Article 1088. https://doi.org/10.1038/s41467-023-36780-x