Some people recover well from traumatic experiences, whereas others may find themselves trapped in cycles of depression that drain happiness from their lives.
Researchers at UCSF have identified a neurological pattern linked to resilience in mice, which could lead to new treatments for severe depression.
While some individuals are able to recover from trauma, others may end up stuck in depressive cycles that diminish their happiness.
Researchers at UC San Francisco are investigating how the brain fosters these different responses, with the aim of helping those who endure long-lasting stress symptoms.
The study revealed that stress affects brain circuitry in mice, helping to differentiate between those that will recover and those that won’t.
By stimulating specific neurons in the less resilient mice to increase their firing rate, the researchers observed that these mice stopped their negative thought patterns and actively sought out enjoyable experiences, such as drinking sugar-sweetened water.
Mazen Kheirbek, PhD, an associate professor of psychiatry and the study’s senior author, stated, “This finding indicates that if we can recalibrate these brain signals in mice, a similar approach could potentially work as an antidepressant in humans,” with the study being published in Nature on December 4.
The stress of indecision
Kheirbek, a member of the UCSF Weill Institute for Neurosciences, collaborated with a team that included Frances Xia, PhD, a psychiatry associate specialist at UCSF, along with Valeria Fascianelli, PhD, and Stefano Fusi, PhD, from Columbia University.
The researchers focused on the amygdala, a brain region crucial for assessing the risk of pursuing rewards.
Initially, they monitored brain activity while the mice rested. They found that stress significantly altered the amygdala activity in the less resilient mice compared to the more resilient ones.
When given a choice between plain and sugar-sweetened water, resilient mice quickly went for the sugary option.
In contrast, the less resilient mice became fixated and often chose the plain water instead.
Xia analyzed the brain recordings from the mice that opted for the sweet water and discovered that their amygdala communicated effectively with the nearby hippocampus, which is involved in memory and prediction.
Conversely, the mice that couldn’t decide between the two water options exhibited disrupted communication between these brain regions.
Connecting the dots
Xia hypothesized that by stimulating the neurons connecting the amygdala and hippocampus more frequently, she could reduce rumination and enhance decision-making in the mice.
To achieve this, she utilized a method known as chemogenetics, which leverages artificial molecules to interact within the body.
The team added a receptor molecule to the surface of hippocampal neurons to encourage them to fire.
Then, Xia injected the less resilient mice with a second molecule that would bind to this receptor, prompting the neurons to activate.
When presented with the choice of water again, these mice chose the sweeter option, and their brain activity indicators appeared to reflect resilience.
“It felt like such a far-fetched idea that I could hardly believe it succeeded,” Xia remarked. “This process effectively eliminated their indecision and transformed these mice into resilient ones.”
The research team intends to analyze human brain data to search for comparable patterns.
Kheirbek is collaborating with specialists at the Dolby Family Center for Mood Disorders to investigate various techniques for modifying these brain functions.
“There is significant interest in discovering how to apply these findings to develop effective treatments for people,” he stated. “If we succeed, we could establish a new, non-invasive method for addressing depression.”
