Understanding how endocannabinoids in the brain help extinguish fear

2023

Challenge

Stress-related neuropsychiatric disorders, such as post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), may be characterized by fears or intrusive thoughts and behaviors that are extremely difficult to stop. The ability to end these reactions, which psychiatrists call ‘extinction,’ is impaired in these disorders. Chemicals called endocannabinoids (eCBs) that occur naturally in the body and influence brain activity have been shown to be involved in fear extinction, but the precise mechanism for how they do this has remained unclear.

Advance

IRP researchers led by Andrew Holmes, Ph.D., showed in mice how eCBs influenced the activity of a neuronal signaling pathway connecting the brain’s prefrontal cortex and amygdala, two brain regions linked to fear extinction. The study’s results showed that fear extinction was associated with an increase in eCBs at the connection points, called synapses, where neurons from the prefrontal cortex and amygdala meet. Furthermore, the study showed that loss of eCB-induced signaling at these synapses impaired fear extinction.

Impact

These findings provide new insight into how eCBs operate at these key brain circuits to produce their extinction-promoting effects. In doing so, the study will inform efforts to develop novel therapeutic approaches that target the brain’s eCB signaling system to treat the fear extinction deficiencies found in many psychiatric illnesses.

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