Neuronal structural plasticity gives the adult brain the capacity to adapt to internal or external factors by structural and molecular changes. These plastic processes seem to be mediated, among others, by the action of the neurotransmitter serotonin through specific receptors (5-HTRs). Previous studies have shown that the maturation of granule cells in the hippocampus is mediated by 5-HT3. In the present study, we wanted to check if the neural maturation in layer II piriform cortex is also mediated by 5-HT3. In the piriform cortex, in contrast to the hippocampus, there is no postnatal neurogenesis. All immature neurons (PSA-NCAM immunoreactive) were originated prenatally. Immature cells in this area begin as small cells (type I cells) that then mature to larger cells (type II cells), and finally, mature to principal cells (PSA-NCAM immunonegative). To study the role of 5HT3 in this population, we first demonstrated the presence of 5HT3 receptors on both type I and II cells. Then we increased serotonin concentration using chronic fluoxetine administration, producing a reduction in the number of type I cells and an increment of type II cells but not an induction in the final stage of maturation to principal cells, as shown by the higher number of immature cells than in controls. This effect was blocked by ondansetron (a 5 HT3 antagonist). In conclusion, serotonin induces the progression from type I cells to type II cells but not from the later to mature PSA-NCAM immunonegative neurons. This effect is mediated by 5-HT3 receptors present in the immature cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)