Region- and Layer-Specific Glutamatergic Synapse Development in the Nascent Cortical Hierarchy.

Neocortical synapses are highly dynamic during brain development, undergoing formation, elimination, and maturation before acquiring properties that support adult cognition. Individual neocortical regions develop at different ages, and individual layers within these regions contain distinct neuronal subtypes that process unique patterns of local and long-range synaptic input. To better understand the development of the cortical hierarchy, we explored the laminar maturation of glutamatergic synapses across cortical regions of male and female mice. Synapse maturation was associated with the upregulation of the postsynaptic density protein PSD95. This maturation occurred in a region- and layer-specific manner-layers associated with feedforward pathways develop earlier, while layers associated with higher-order circuits develop later. Our findings highlight adolescence as an important period for the cortex-wide maturation of synapses in cortical layer 1, synapses known to receive top-down feedback from higher-order cortices. We propose that this delayed adolescent maturation of top-down input represents a global signature of cortical development and seemingly acts as the final stage of outside-in brain maturation.