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.
Keywords: endocannabinoid; hippocampus; iLTD; n-3 PUFA; synaptic plasticity.
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