Positive early-life olfactory memory is rooted in the olfactory bulb and triggers large-scale changes beyond the olfactory system

Olfactory childhood memories are particularly important for forming one’s identity. However, we don’t know how they exert their privileged influence and shape brain structure. To address this, we modeled childhood olfactory memory in mice based on a human survey indicating that our earliest olfactory memory arises from repeated positive experiences paired with a pleasant odorant. Accordingly, mice were exposed during childhood to an attractive odorant in a playful environment. In adulthood, memory recall relied on neonatal-born granule cells (GCs) in the olfactory bulb, as their optogenetic silencing impaired retrieval, and on increased functional connectivity in the reward system. With age, memory persistence depended on re-exposure to the childhood odorant and was associated with the disengagement of neonatal-born GCs, alongside with strengthened limbic functional connectivity. Together, these findings identify neonatal neurons as a key substrate for encoding childhood olfactory memory and reveal dynamic reorganization of brain networks supporting its long-term significance.