Opioid modulation of Fos protein expression and olfactory circuitry plays a pivotal role in what neonates remember.

Paradoxically, fear conditioning (odor-0.5 mA shock) yields a learned odor preference in the neonate, presumably due to a unique learning and memory circuit that does not include apparent amygdala participation. Post-training opioid antagonism with naltrexone (NTX) blocks consolidation of this odor preference and instead yields memory of a learned odor aversion. Here we characterize the neural circuitry underlying this switch during memory consolidation. Experiment 1 assessed post-training opioid modulation of Fos protein expression within olfactory circuitry (olfactory bulb, piriform cortex, amygdala). Odor-shock conditioning with no post-training treatment (odor preference) induced significant changes in Fos protein expression in the granule cell layer of the olfactory bulb and anterior piriform cortex. Post-training opioid receptor antagonism (odor aversion) prevented the learning-induced changes in the anterior piriform cortex and also induced significant changes in Fos protein expression in the central nucleus of the amygdala. Experiment 2 assessed intra-amygdala opioid modulation of neonate memory consolidation. Post-training infusion of NTX within the amygdala permitted consolidation of an odor aversion, while vehicle-infused pups continued to demonstrate an odor preference. Overall, results demonstrate that opioids modulate memory consolidation in the neonate via modulating Fos protein expression in olfactory circuitry. Furthermore, these results suggest that opioids are instrumental in suppressing neonate fear behavior via modulating the amygdala.