LAUSR

Abstract Maternal n‐3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, is critical during perinatal brain development. How early postnatal n‐3 PUFA deficiency impacts on hippocampal synaptic plasticity is mostly unknown. Here we compared activity‐dependent plasticity at excitatory and inhibitory synapses in the CA1 region of the hippocampus in weaned pups whose mothers were fed with an n‐3 PUFA‐balanced or n‐3 PUFA‐deficient diet. Normally, endogenous cannabinoids (eCB) produced by the post‐synapse dually control network activity by mediating the long‐term depression of inhibitory inputs (iLTD) and positively gating NMDAR‐dependent long‐term potentiation (LTP) of excitatory inputs. We found that both iLTD and LTP were impaired in n‐3 PUFA‐deficient mice. Pharmacological dissection of the underlying mechanism revealed that impairment of NMDAR‐dependent LTP was causally linked to and attributable to the ablation of eCB‐mediated iLTD and associated to disinhibitory gating of excitatory synapses. The data shed new light on how n‐3 PUFAs shape synaptic activity in the hippocampus and provide a new synaptic substrate to the cognitive impairments associated with perinatal n‐3 deficiency.