Microglial activation enhances associative taste memory through purinergic modulation of glutamatergic neurotransmission

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.

Keywords: AMPA; ATP; cytokines; lipopolysaccharide; neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Association Learning / drug effects
  • Association Learning / physiology*
  • Corticosterone / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalitis / blood
  • Encephalitis / chemically induced
  • Encephalitis / physiopathology*
  • Glutamic Acid / metabolism
  • Lipopolysaccharides / pharmacology
  • Lithium Chloride / pharmacology
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Microglia / drug effects
  • Microglia / metabolism*
  • Protein Transport / drug effects
  • Purinergic Agents*
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Taste / drug effects
  • Taste / physiology*


  • Cytokines
  • Lipopolysaccharides
  • NR2B NMDA receptor
  • Purinergic Agents
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Lithium Chloride
  • glutamate receptor ionotropic, AMPA 2
  • Corticosterone