Stress is not one-size-fits-all: stressor-specific effects on learning and memory in a molluscan model

Environmental stressors profoundly influence how animals learn and remember, yet different types of stress can trigger distinct behavioural and molecular outcomes. Understanding this is essential for decoding adaptive responses in ecological settings and also for informing translational models of stress-related cognitive dysfunction. The pond snail Lymnaea stagnalis offers a powerful platform for such investigations. Despite their simplicity compared to mammals, they exhibit higher-order associative learning, such as the Garcia effect, where a novel taste cue, when associated over a time gap (which can be hours) with sickness (induced by acute heat shock), causes the snails to avoid the novel food. The snails also show configural learning, which occurs when a positive (food cue) and negative stimulus (predator odour) are presented simultaneously, leading to the formation of a ‘fear landscape’, and the consequent avoidance of the positive food cue. In this study, we extend these existing paradigms by using biologically relevant stressors: a predator-attack-mimicking shell clip (ShC) and acute heat shock (HS). We found striking, stressor-specific differences in behavioural outcomes: ShC supported configural learning but not the Garcia effect, while HS induced the Garcia effect but failed to support configural learning. Along with behaviour, we show distinct transcriptional changes in the central ring ganglia, affecting expression levels of key targets including stress- and plasticity-related genes, serotonergic markers and enzymes of the endocannabinoid system. Together, these results suggest that different stressors establish unique internal stress states (‘fear’ versus ‘sickness’) that selectively shape learning pathways. This study highlights a critical principle in neuroscience: stress is not a monolith, and its impact on learning and memory depends on both its nature and the internal state it evokes. This finding holds direct relevance for understanding stress-related psychiatric disorders and maladaptive behaviours. • Stressor type determines if snails form configural learning or the Garcia effect. • Shell clip enables configural learning and heat shock supports the Garcia effect. • Stressors produce distinct transcriptional profiles in central ring ganglia. • Changes involve stress-, plasticity-, serotonin- and endocannabinoid-related genes. • The impact of stress on memory depends on the internal state produced.