Non-newly generated, "immature" neurons in the sheep brain are not restricted to cerebral cortex

A newly proposed form of brain structural plasticity consists of non-newly generated, "immature" neurons of the adult cerebral cortex. Similar to newly generated neurons, these cells express the cytoskeletal protein Doublecortin (DCX), yet they are generated prenatally, then remaining in a state of immaturity for long periods. In rodents, the immature neurons are restricted to the paleocortex, whereas in other mammals are found also in neocortex. Here, we analyzed the DCX-expressing cells in the whole sheep brain of both sexes, to search for an indicator of structural plasticity at a cellular level in a relatively large-brained, long-living mammal. Brains from adult and newborn sheep (injected with BrdU and analyzed at different survival times) were processed for DCX, cell proliferation markers (Ki-67, BrdU), pallial/subpallial developmental origin (Tbr1, Sp8), and neuronal/glial antigens for phenotype characterization. We found immature-like neurons in the whole sheep cortex and in large populations of DCX-expressing cells within the external capsule and the surrounding grey matter (claustrum and amygdala). BrdU and Ki-67 detection at neonatal and adult ages showed that all these DCX+ cells were generated during embryogenesis, not after birth. These results show that the adult sheep, unlike rodents, is largely endowed with non-newly generated neurons retaining immature features, suggesting that such kind of plasticity might be particularly important in large brained, long living mammals.