Delpech Jean-Christophe, Saucisse Nicolas, Parkes Shauna L, Lacabanne Chloe, Aubert Agnes, Casenave Fabrice, Coutureau Etienne, Sans Nathalie, Layé Sophie, Ferreira Guillaume, Nadjar Agnes
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.
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.
J Neurosci. 2015 Feb 18;35(7):3022-33. doi: 10.1523/JNEUROSCI.3028-14.2015.
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.
大脑先天性免疫系统能够调节大脑功能和认知过程。在大脑先天性免疫系统激活期间，小胶质细胞产生的炎症因子，如细胞因子和三磷酸腺苷（ATP），一方面与谷氨酸能系统的调节直接相关，另一方面与学习和记忆功能直接相关。然而，小胶质细胞激活调节认知过程的细胞机制仍不清楚。在此，我们利用高度依赖岛叶皮质谷氨酸能传递的味觉记忆任务，来研究局限于该皮质区域的炎症对大鼠行为和细胞的影响。我们首先表明，向岛叶内注射内毒素脂多糖会引发局部炎症，并在突触水平增加谷氨酸能AMPA受体而非NMDA受体的表达。这种皮质炎症还通过增加谷氨酸能AMPA受体的转运来增强关联性味觉记忆，而非偶发性味觉记忆。此外，我们证明，是ATP而非促炎细胞因子导致了岛叶皮质中炎症诱导的关联性味觉记忆增强和AMPA受体表达增加。总之，我们提出，局限于岛叶皮质的炎症通过突触处谷氨酸能AMPA受体表达的嘌呤能依赖性增加来增强关联性味觉记忆。
