Correct Laminar Positioning in the Neocortex Influences Proper Dendritic and Synaptic Development

The neocortexis a six-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neuronsby knocking down Dcx, a crucial effector of migration, and show that misplaced neuronsfail to properly form dendrites, spinesand functional glutamatergicsynapses. We further show that knocking down Dcx in properly positioned neuronsinduces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronaldevelopment. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integrationinto developing cortical circuits.