Agnès Nadjar, Guillaume Ferreira et al. inThe J of N

Agnès Nadjar et Guillaume Ferreira  co-dernier auteurs. (INRA, Nutrition et neurobiologie intégrée, UMR 1286 NutriNeurO)

Microglial Activation Enhances Associative Taste Memory through Purinergic Modulation of Glutamatergic Neurotransmission
Jean-Christophe Delpech, Nicolas Saucisse, Shauna L. Parkes, Chloe Lacabanne, Agnes Aubert, Fabrice Casenave, Etienne Coutureau, Nathalie Sans, Sophie Laye ́, Guillaume Ferreira, Agnes Nadjar. The Journal of Neuroscience, February 18, 2015 • 35(7):3022–3033 / Neurobiology of Disease

The Biochemistry and Biophysics Facility of the Bordeaux Neurocampus is supported by the LABEX BRAIN  

In the condition of neuroinflammation, the delicate physiological balance between immune and neural processes is disrupted, leading to changes in neuroplasticity, learning, and memory. Recent studies suggest that neuroinflammation affects the glutamatergic system but a clear demonstration that the cognitive alterations induced by neuroinflammation involve the glutamatergic system is still lacking. Our challenge was to answer this question. We used taste memory tasks, highly dependent on glutamatergic transmission in the insular cortex, to investigate the behavioral and cellular impact of an inflammation restricted to this cortical area in rats. We first showed that intra-insular infusion of the endotoxin lipopolysaccharide induces a local inflammation and increases glutamatergic AMPA, but not NMDA, receptor expression at the synapse. This cortical inflammation also enhances associative, but not incidental, taste memory through increase of glutamatergic AMPA receptor trafficking. We also found that ATP was responsible for the biochemical and behavioral effects of localized inflammation. 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. Our data represent the first in vivo study demonstrating a causal link between neuroinflammation-induced modulation of glutamatergic transmission and memory involving ATP as a key mediator of these neuronal and behavioral alterations.

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 inflamma- tion 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.

Key words: AMPA; ATP; cytokines; lipopolysaccharide; neuroinflammation