NMDAR-dependent proteasome activity in the gustatory cortex is necessary for conditioned taste aversion.

Taste information is processed in different brain structures in the mammalian brain, including the gustatory cortex (GC), which resides within the insular cortex. N-methyl-d-aspartate receptor (NMDAR) activity in the GC is necessary for the acquisition of conditioned taste aversion (CTA) but not positive novel taste learning. Previous studies have shown that taste memory consolidation requires intact protein synthesis in the GC. In addition, the direct involvement of translation initiation and elongation factors was documented in the GC during taste learning. However, protein expression is defined by protein synthesis, degradation, and localization. Protein degradation is critical for the consolidation and reconsolidation of other forms of learning, such as fear learning and addiction behavior, but its role in cortical-dependent learning is not clear. Here, we show for the first time that proteasome activity is specifically increased in the GC 4h following experiencing of a novel taste. This increase in proteasome activity was abolished by local administration to the GC of the NMDA antagonist, APV, as well as a CaMKII inhibitor, at the time of acquisition. In addition, local application of lactacystin, a proteasome inhibitor, resulted in impaired CTA, but not novel taste learning. These results suggest that NMDAR-dependent proteasome activity in the GC participates in the association process between novel taste experience and negative visceral sensation.