New Discovery on Brain’s Chemical Communication
Researchers from the Hebrew University of Jerusalem and SUNY Stony Brook University have made an exciting finding: one chemical signaling system in the brain can effectively dominate another. This discovery sheds light on the roots of chemical imbalances linked to various challenging neurological and psychiatric conditions, including Parkinson’s disease, OCD, anxiety, and depression.
Prof. Joshua Goldberg from Hebrew University and Prof. Joshua Plotkin from Stony Brook led this study, focusing on the dorsal striatum—a critical area for learning and movement. They explored how coordination between brain cells might sometimes become hyperactive.
Goldberg explained that compulsive behaviors like excessive checking or washing likely stem from unusual activity in the dorsal striatum’s circuits, which govern habitual actions. Using AI alongside advanced imaging methods in pre-clinical trials on mice, the team investigated the influence of acetylcholine, a brain chemical known to stimulate serotonin release—a neurotransmitter closely associated with mood regulation and psychiatric disorders.
The recently published findings in Nature Communications provide insights into why certain behaviors can be “so hard to stop” in conditions such as OCD. Goldberg emphasized that understanding these interactions might help clarify the underlying dysfunction in circuits responsible for these disorders, potentially leading to new treatment pathways.
OCD: A Global Psychiatric Concern
Plotkin noted that OCD is among the most prevalent psychiatric disorders, affecting up to three percent of the global population, cutting across various nationalities, races, and genders. In Israel, a study highlighted the impact of acute trauma on OCD symptoms. Following the traumatic events of the October 7, 2023, Hamas attack, nearly 40 percent of those exposed developed symptoms consistent with OCD, compared to just seven percent of a control group.
Behaviors related to OCD described in this context included compulsive cleaning and repeatedly checking locks and doors, often driven by fears regarding safety.
The Brain’s Decision-Making Process
Plotkin’s research is focused on how the brain meticulously considers myriad potential actions, distinguishing between appropriate and inappropriate responses. He suggested that failures in this decision-making process underlie many neurological disorders, notably OCD.
Goldberg highlighted that, while many researchers concentrate on genetic factors or specific molecules, their focus is on how brain circuit activity is altered in various diseases. The collaboration between the two scientists has spanned several years, including joint research since 2017.
The basal ganglia, particularly the striatum, plays a vital role in habit learning and action selection. It serves as the main hub for information from different brain areas, sorting through inputs before determining actions. Within this network, acetylcholine acts as a messenger between nerve cells.
Goldberg noted a longstanding acknowledgment among neuroscientists regarding the interaction between the acetylcholine system and the dopamine system—a chemical essential for reward and learning. These connections were previously hinted at in research but not thoroughly explored until now, allowing them to make significant advances.
Investigating Acetylcholine and Dopamine Dynamics
Utilizing optogenetics—technology that lets researchers control specific brain cells with light—the team found that stimulating acetylcholine cells led to an immediate response from serotonin fibers, essentially demonstrating that acetylcholine could take charge of the serotonin release.
During their observations of brain states associated with OCD, the team discovered that acetylcholine cells were overactive, resulting in a marked increase in serotonin. This finding implies that OCD symptoms may arise from a coordination failure rather than merely an excess of one chemical.
Goldberg mentioned that the surprising aspect of their discovery was the interaction between acetylcholine and serotonin occurring in areas of the brain typically characterized by sparse serotonin input, yet likely playing a significant role in disorders involving compulsive behavior.
Jun Ding, a neurology professor at Stanford University, commented on the study’s novelty, noting its insights into how specific neurons using acetylcholine can directly activate serotonin release and how this dynamic strengthens in OCD models.
Goldberg said that this interaction raises numerous questions about how these circuits operate and malfunction. Plotkin’s lab is already collaborating with others at Stony Brook to lay the groundwork for clinical trials examining acetylcholine’s role.
With current treatment options for OCD still lacking, Plotkin expressed the urgent need for better-targeted therapies. The insights gained from this research may hold vital clues for developing more effective treatments moving forward.
