Pheromone-induced odor learning modifies Fos expression in the newborn rabbit brain

Associative learning contributes crucially to adjust the behavior of neonates to the permanently changing environment. In the European rabbit, the mammary pheromone (MP) excreted in milk triggers sucking behavior in newborns, and additionally promotes very rapid learning of initially neutral odor cues. Such stimuli become then as active as the MP itself to elicit the orocephalic motor responses involved in suckling. In this context, the rabbit is an interesting model to address the question of brain circuits early engaged by learning and memory. Here, we evaluated the brain activation (olfactory bulb and central regions) induced in 4-day-old pups by an odorant (ethyl acetoacetate, EAA) after single pairing with the MP and its subsequent acquired ability to elicit sucking-related behavior (conditioned group) or after mere exposure to EAA alone (unconditioned group). The brain-wide mapping of c-Fos expression was used to compare neural activation patterns in both groups. Evidence of high immunostaining to odorant EAA occurred in the mitral+granule cells layer of the main olfactory bulb in pups previously exposed to EAA in association with the MP. These pups also showed higher expression of Fos in the piriform cortex, the hypothalamic lateral preoptic area and the amygdala (cortical and basal nuclei). Thus, MP-induced odor learning induces rapid brain modifications in rabbit neonates. The cerebral framework supporting the acquisition appears however different compared to the circuit involved in the processing of the MP itself.