Immature Neurons in the Postnatal Brain: Markers, Modulation, and Involvement in Normal and Aberrant Plasticity

Cortical immature neurons (cINs) represent a unique population of prenatally generated, non-dividing neurons that maintain an immature phenotype, characterized by doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) expression, into adulthood. Unlike canonical adult neurogenesis involving continuous neuron generation from stem cell niches, cINs constitute a distinct form of structural plasticity termed “neurogenesis without division”. This review comprehensively examines the molecular markers, morphological diversity, developmental origins, and maturation trajectories of cINs across species. We highlight the striking inverse interspecies relationship between cIN abundance and canonical adult neurogenesis, reflecting distinct biophysical and structural shifts in neural plasticity mechanisms across mammalian lineages. Furthermore, we discuss factors modulating cIN phenotype, including neurotransmitter systems, stress, sensory experience, and aging. Clinical evidence implicating cIN alterations in temporal lobe epilepsy, traumatic brain injury, and stroke is evaluated, revealing potential roles in both pathological circuit remodeling and endogenous repair. Critical gaps remain regarding the molecular programs maintaining immaturity, differentiation triggers, and the functional consequences of circuit integration. Understanding cIN biology offers new perspectives on cortical plasticity and may inform therapeutic strategies targeting endogenous cellular reserves for brain repair.