Indiana University researchers have discovered that an enzyme involved in producing cannabis-like chemicals in the brain plays a significant role in social behavior and anxiety, findings that challenge long-held views about a part of the brain called the cerebellum. The study focused on Purkinje cells—neurons in the cerebellum traditionally linked to movement and coordination—and examined what happened when the enzyme DAGLα, which produces the endocannabinoid 2-AG, was removed from these cells. The endocannabinoid system, similar to the one that cannabis interacts with, helps neurons adjust their signaling in response to changing conditions, fine-tuning communication in the brain.
Mice lacking the DAGLα enzyme in their Purkinje cells performed unusually well on precise movement tasks but showed reduced social interaction and higher anxiety in novel environments. The researchers also found that without this enzyme, neural communication in the cerebellum was less adaptable, meaning the brain cells couldn’t adjust their signaling strength as effectively—an ability linked to learning, emotional processing, and social behavior. These results suggest the cerebellum influences more than balance and movement, potentially contributing to emotional and social challenges seen in conditions like anxiety and autism spectrum disorder.
By studying mice with DAGLα removed specifically from Purkinje cells, we’re gaining important insights into how changes in cerebellar activity and synaptic plasticity can lead to social and emotional differences,” said the study’s lead author Anna Kalinovsky, Assistant Research Scientist in the Department of Psychological and Brain Sciences within IU’s College of Arts and Sciences and IU’s Gill Institute for Neuroscience. “This research offers a clearer understanding of how disruptions in the brain’s endocannabinoid system might contribute to anxiety and social challenges in humans.
“Understanding this process could one day lead to new treatments that boost endocannabinoid signals in specific parts of the brain to reduce anxiety or improve social functioning,” said Ken Mackie, Distinguished Professor of Psychological and Brain Sciences and a Linda and Jack Gill Chair in IU’s Gill Institute for Neuroscience. “It could also help doctors identify and support children with genetic variations that affect DAGLα earlier in life.”