title: Nutritional n-3 PUFA Deficiency Abolishes Endocannabinoid Gating of Hippocampal Long-Term Potentiation.
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.
authors.affiliation: Nutrition et Neurobiologie Intégrée, UMR 1286, INRA, F-33000 Bordeaux, France.|Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux University, F-33000 Bordeaux, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Thomazeau
authors.affiliation: Nutrition et Neurobiologie Intégrée, UMR 1286, INRA, F-33000 Bordeaux, France.|Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux University, F-33000 Bordeaux, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Bosch-Bouju
authors.affiliation: Aix-Marseille Université.|INSERM.|INMED UMR S 901, Marseille 13009, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Manzoni
authors.affiliation: Nutrition et Neurobiologie Intégrée, UMR 1286, INRA, F-33000 Bordeaux, France.|Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux University, F-33000 Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
mesh_terms: D000818:Animals; D063388:Endocannabinoids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D039401:Prenatal Nutritional Physiological Phenomena
chemical_list: D063388:Endocannabinoids; D015525:Fatty Acids, Omega-3
keywords: endocannabinoid; hippocampus; iLTD; n-3 PUFA; synaptic plasticity