Memory formation following appetitive conditioning is variably dependent on retinoid signaling

Abstract

Retinoic acid (RA), the metabolite of Vitamin A, plays an important role in central nervous system development and regeneration, as well as learning and memory in vertebrates. We have previously shown that RA signaling is also important for consolidation of long-term memory (LTM) in the invertebrate mollusc, Lymnaea stagnalis, following operant conditioning of the aerial respiratory behaviour. Here, we examine whether retinoids also play a role in classical reward conditioning in this mollusc. A single-trial appetitive conditioning paradigm was used, with amyl acetate as the conditioned stimulus (CS) and sucrose as the unconditioned stimulus (US). This produced an acquired conditioned response whereby the animal exhibited a feeding response to amyl acetate. A single-pairing of CS with US produced long-term memory at both 1d and 6d after training. Pharmacological treatments that disrupt RA signaling did not block the formation of long term memory when a 6-day food deprivation period was implemented before training. However, two different paradigms induced susceptibility of the conditioned response (memory) to retinoid signaling inhibitors. The first paradigm change involved using a shorter, 3-day food deprivation period in order to reduce motivational drive to feed, whereas the second paradigm manipulation reduced the strength of the unconditioned stimulus (sucrose). These findings suggest different susceptibility of memories to retinoid inhibition, depending on shifts in both external parameters of the experiment, as well as internal motivational states of the animal.