The role of depressive symptoms, episodic memory, and executive functioning on prospective memory: new insights from the Canadian Longitudinal Study on Aging.

Our findings provide a high-throughput analysis of the postnatal development of glutamatergic synaptic proteins across the neocortical hierarchy. We highlight key differences in the maturation of higher cognitive areas and sensory–motor areas. We also observe the delayed and protracted maturation of cortical layer (L)1, which develops in a neocortex-wide manner during adolescence. Using analysis of synaptic puncta and computational modeling, we explore the synaptic mechanisms that underlie these changes. This work highlights adolescence as an important period for the maturation of top–down inputs to L1, which may play an important role in the emergence of adult-like cognition during this developmental stage. The neocortex is organized hierarchically, with sensory regions at the bottom and association cortices at the top (). The canonical view is that brain development mirrors this hierarchy, with sensory regions maturing prior to association areas across species (; ). However, evidence from primates and rodents challenges this idea, suggesting the maturation of sensory and association areas is remarkably similar (; ). Cortical maturation has predominantly been studied in primary sensory circuits due to the ease with which sensory afferents can be manipulated (). These studies indicate that development follows the canonical cortical microcircuit (; ), with sensory critical periods occurring first in thalamocortical synapses and then within layer (L)4, followed by the ascending L4→L2/3 pathway and L2/3 recurrent synapses (). This sequential maturation is termed “outside–in,” whereby critical periods occur along the arc of sensory information transfer from the periphery to the neocortex (; ). If, or how, layer-specific maturation occurs in higher-order regions remains to be determined. Brain development culminates in adolescence when higher-order brain regions, including the prefrontal cortex (PFC), undergo final maturation (; ; ). This process supports the acquisition of adult-like cognition (; ) and likely contributes to the increased susceptibility of the adolescent brain to neuropsychiatric and mental health conditions (; ). Despite its clear importance, less is known about PFC maturation. PFC thalamic input is present from the first postnatal week in rodents (). Neural activity during this time is important for network formation and function () and depends on preconfigured synaptic parameters (). Subsequent thalamic activity orchestrates adult-like connectivity and cognition (; ; ). However, it is unclear if the PFC undergoes thalamus-first maturation, mirroring sensory cortices, or if its distinct architecture () gives rise to alternative layer- or input-specific development (; ).