Abstract: Brain plasticity—A universal tool with many variations: The study of brain plasticity has been gaining interest since almost a century and has now reached a huge amount of information (> 80,000 results in PubMed). Overall, different types of plasticity, including stem cell-driven genesis of new neurons (adult neurogenesis), cells in arrested maturation (dormant neurons), neuro-glial and synaptic plasticity, can coexist and contribute to grant plastic changes in the brain, from a cellular to system level (Benedetti and Couillard-Despres, 2022; Bonfanti et al., 2023). Most of the current knowledge is based on laboratory rodents and largely deals with cellular and molecular mechanisms aimed at exploiting a potential for brain repair. Comparative approaches have also been used, spanning from simple organisms (e.g., drosophila, zebrafish) to the direct study of human brains (either on postmortem tissue or through non-invasive imaging). The finding of common aspects in the entire animal world leads to consider neural plasticity as a shared biological tool to allow structural and functional changes as an adaptive mechanism. Conversely, due to adaptation itself, different types of plasticity emerged in animal groups living in widely different ecological niches (Barker et al., 2011). Consequently, the occurrence of the main types of plastic changes (i.e., synaptic plasticity, adult neurogenesis, and immature, or “dormant” neurons; Benedetti and Couillard-Despres, 2022; Bonfanti et al., 2023) can remarkably vary depending on the animal species or age considered, regarding their anatomical location, spatial extension, and rate (Paredes et al., 2016; La Rosa et al., 2020; Figure 1A). For instance, the genesis of new neurons is abundant, topographically widespread, and consistent through the lifespan in fish, whereas it appears quite reduced in mammals, both in space and time (Bonfanti, 2011). Another important difference between non-mammalian and mammalian brain plasticity concerns its ultimate role, which encompasses striking regenerative processes allowing brain repair in the former, while being mostly aimed at refining the neural circuits through postnatal brain development in the latter (Bonfanti, 2011). Though the different types of brain plasticity can be found in all species, comparative research started to reveal significant variation among mammals, particularly concerning different types of neurogenic processes (with and without division; Benedetti and Couillard-Despres, 2022) that can show either high or low rates depending on brain size, gyrencephaly, and longevity of the species considered (Bonfanti et al., 2023). These interspecies variations underline the notion that plasticity is not a brain function, rather a tool that can be used to perform remarkably differing functions among animal species (Barker et al., 2011). There are multiple explanations for the adaptive significance of adult neurogenesis and how particular ecological needs and evolutionary pathways have directed its function in each animal group. These adaptive processes are at the basis of a trade-off in different types of plasticity, determining a high interspecies heterogeneity that must be known for the correct translation of experimental results obtained in laboratory rodents (Bonfanti et al., 2023). In summary, besides data indicating evolutionary conservation of cellular/molecular mechanisms and local circuit connectivity motifs in mice and humans, the existence of remarkable differences in neuroanatomy, global connectivity, and, particularly, neurogenic plasticity, increases the need for multispecies comparative studies (Bonfanti et al., 2023; Figure 1A). Yet, such kind of approach, in addition to obvious technical and ethical difficulties, entails the problem of obtaining comparable results.