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.

Multisensory integration supports configural learning of a home refuge in the whip spider Phrynus marginemaculatus

ABSTRACTWhip spiders (Amblypygi) reside in structurally complex habitats and are nocturnally active yet display notable navigational abilities. From the theory that uncertainty in sensory inputs should promote multisensory representations to guide behavior, we hypothesized that their navigation is supported by a multisensory and perhaps configural representation of navigational inputs, an ability documented in a few insects and never reported in arachnids. We trained Phrynus marginemaculatus to recognize a home shelter characterized by both discriminative olfactory and tactile stimuli. In tests, subjects readily discriminated between shelters based on the paired stimuli. However, subjects failed to recognize the shelter in tests with either of the component stimuli alone. This result is consistent with the hypothesis that the terminal phase of their navigational behavior, shelter recognition, can be supported by the integration of multisensory stimuli as an enduring, configural representation. We hypothesize that multisensory learning occurs in the whip spiders' extraordinarily large mushroom bodies, which may functionally resemble the hippocampus of vertebrates.

Elemental and Configural Associative Learning in Spatial Tasks: Could Zebrafish be Used to Advance Our Knowledge?

Spatial learning and memory have been studied for several decades. Analyses of these processes pose fundamental scientific questions but are also relevant from a biomedical perspective. The cellular, synaptic and molecular mechanisms underlying spatial learning have been intensively investigated, yet the behavioral mechanisms/strategies in a spatial task still pose unanswered questions. Spatial learning relies upon configural information about cues in the environment. However, each of these cues can also independently form part of an elemental association with the specific spatial position, and thus spatial tasks may be solved using elemental (single CS and US association) learning. Here, we first briefly review what we know about configural learning from studies with rodents. Subsequently, we discuss the pros and cons of employing a relatively novel laboratory organism, the zebrafish in such studies, providing some examples of methods with which both elemental and configural learning may be explored with this species. Last, we speculate about future research directions focusing on how zebrafish may advance our knowledge. We argue that zebrafish strikes a reasonable compromise between system complexity and practical simplicity and that adding this species to the studies with laboratory rodents will allow us to gain a better understanding of both the evolution of and the mechanisms underlying spatial learning. We conclude that zebrafish research will enhance the translational relevance of our findings.

Multisensory Configural Learning of a Home Refuge in the Whip Spider Phrynus marginemaculatus

ABSTRACTWhip spiders (Amblypygi) reside in structurally complex habitats and are nocturnally active yet display notable navigational abilities. From the theory that uncertainty in sensory inputs should promote multisensory representations to guide behavior, we hypothesized that their navigation is supported by a configural, multisensory representation of navigational inputs, an ability documented in a few insects and never reported in arachnids. We trained Phrynus marginemaculatus to recognize a home shelter characterized by both discriminative olfactory and tactile stimuli. In tests, subjects readily discriminated between shelters based on the paired stimuli. However, subjects failed to recognize the shelter in tests with either of the component stimuli alone. This result is consistent with the hypothesis that the terminal phase of their navigational behavior, shelter recognition, can be supported by the integration of multisensory stimuli as a configural representation. We hypothesize that multisensory configural learning occurs in the whip spiders’ extraordinarily large mushroom bodies, which may functionally resemble the hippocampus of vertebrates.