Gene expression-based modeling of human cortical synaptic density

Abstract

Postnatal cortical synaptic development is characterized by stages of exuberant growth, pruning, and stabilization during adulthood. How gene expression orchestrates these stages of synaptic development is poorly understood. Here we report that synaptic growth-related gene expression alone does not determine cortical synaptic density changes across the human lifespan, but instead, the dynamics of cortical synaptic density can be accurately simulated by a first-order kinetic model of synaptic growth and elimination that incorporates two separate gene expression patterns. Surprisingly, modeling of cortical synaptic density is optimized when genes related to oligodendrocytes are used to determine synaptic elimination rates. Expression of synaptic growth and oligodendrocyte genes varies regionally, resulting in different predictions of synaptic density among cortical regions that concur with previous regional data in humans. Our analysis suggests that modest rates of synaptic growth persist in adulthood, but that this is counterbalanced by increasing rates of synaptic elimination, resulting in stable synaptic number and ongoing synaptic turnover in the human adult cortex. Our approach provides a promising avenue for exploring how complex interactions among genes may contribute to neurobiological phenomena across the human lifespan.