Long term memory of configural learning is enhanced via CREB upregulation by the flavonoid Quercetin in Lymnaea stagnalis

Animals respond to acute stressors by modifying their behaviour and physiology. The pond snail Lymnaea stagnalis exhibits configural learning (CL), a form of higher order associative learning. In CL snails develop a landscape of fear when they experience a predatory cue along with a taste of food. This experience results in a suppression of the food response; but the memory only persists for 3h. Lymnaea has been also found to upregulate heat shock proteins (HSPs) as a result of acute heat stress that leads to the enhancement of memory formation. A plant flavonoid quercetin blocks the upregulation of HSPs when experienced prior to heat stress. Here we used this blocking mechanism to test the hypothesis that HSP upregulation played a critical role in CL. Snails experienced quercetin prior to CL training and surprisingly instead of blocking memory formation it enhanced the memory such that it now persisted for at least 24h. Quercetin exposure both prior to or post CL enhanced long-term memory (LTM) up to 48h. We quantified CREB1 mRNA levels in the Lymnaea central nervous system following quercetin and found LymCREB1 to be upregulated following quercetin exposure. The enhanced LTM phenotype in L. stagnalis was most pronounced when quercetin was experienced during the consolidation phase. Additionally, quercetin exposure during the memory reconsolidation phase also led to memory enhancement. Thus, we found no support of our original hypothesis but found that quercetin exposure upregulated LymCREB1 leading to LTM formation for CL.