Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions

Lafourcade et al . find that a lifelong insufficiency in dietary n-3 polyunsaturated fatty acids leads to a specific loss of long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens in mice. This was associated with impaired emotional behavior. The corollaries of the obesity epidemic that plagues developed societies are malnutrition and resulting biochemical imbalances. Low levels of essential n-3 polyunsaturated fatty acids (n-3 PUFAs) have been linked to neuropsychiatric diseases, but the underlying synaptic alterations are mostly unknown. We found that lifelong n-3 PUFAs dietary insufficiency specifically ablates long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens. In n-3–deficient mice, presynaptic cannabinoid CB 1 receptors (CB 1 Rs) normally responding to endocannabinoids were uncoupled from their effector G i/o proteins. Finally, the dietary-induced reduction of CB 1 R functions in mood-controlling structures was associated with impaired emotional behavior. These findings identify a plausible synaptic substrate for the behavioral alterations caused by the n-3 PUFAs deficiency that is often observed in western diets.