title: Microglial activation enhances associative taste memory through purinergic modulation of glutamatergic neurotransmission.
abstract: The cerebral innate immune system is able to modulate brain functioning and cognitive processes. During activation of the cerebral innate immune system, inflammatory factors produced by microglia, such as cytokines and adenosine triphosphate (ATP), have been directly linked to modulation of glutamatergic system on one hand and learning and memory functions on the other hand. However, the cellular mechanisms by which microglial activation modulates cognitive processes are still unclear. Here, we used taste memory tasks, highly dependent on glutamatergic transmission in the insular cortex, to investigate the behavioral and cellular impacts of an inflammation restricted to this cortical area in rats. We first show that intrainsular infusion of the endotoxin lipopolysaccharide induces a local inflammation and increases glutamatergic AMPA, but not NMDA, receptor expression at the synaptic level. This cortical inflammation also enhances associative, but not incidental, taste memory through increase of glutamatergic AMPA receptor trafficking. Moreover, we demonstrate that ATP, but not proinflammatory cytokines, is responsible for inflammation-induced enhancement of both associative taste memory and AMPA receptor expression in insular cortex. In conclusion, we propose that inflammation restricted to the insular cortex enhances associative taste memory through a purinergic-dependent increase of glutamatergic AMPA receptor expression at the synapse.
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Delpech
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Saucisse
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, Centre National de la Recherche Scientifique, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Unité Mixte de Recherche 5287, 33076 Bordeaux, France, Université de Bordeaux, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, 33076 Bordeaux, France.
authors.forename: Shauna L
authors.initials: SL
authors.lastname: Parkes
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France.
authors.forename: Chloe
authors.initials: C
authors.lastname: Lacabanne
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Aubert
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Casenave
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Unité Mixte de Recherche 5287, 33076 Bordeaux, France, Université de Bordeaux, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, 33076 Bordeaux, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Coutureau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U862 NeuroCentre Magendie, Planar Polarity and Plasticity Group, Bordeaux, France, and University of Bordeaux, U862 NeuroCentre Magendie, Bordeaux, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sans
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, guillaume.ferreira@bordeaux.inra.fr agnes.nadjar@u-bordeaux.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ferreira
authors.affiliation: INRA, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, University of Bordeaux, Nutrition et Neurobiologie intégrée, Unité Mixte de Recherche 1286, Bordeaux, France, guillaume.ferreira@bordeaux.inra.fr agnes.nadjar@u-bordeaux.fr.
authors.forename: Agnes
authors.identifier: http://orcid.org/0000-0002-3969-6530
authors.initials: A
authors.lastname: Nadjar
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D058905:Purinergic Agents; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013649:Taste / Q000187:drug effects / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C121001:NR2B NMDA receptor; D058905:Purinergic Agents; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D018021:Lithium Chloride; C104722:glutamate receptor ionotropic, AMPA 2; D003345:Corticosterone
keywords: AMPA; ATP; cytokines; lipopolysaccharide; neuroinflammation