Syngap1 Synchronizes Relative Neuronal Maturation Across Cortical Areas to Organize Distributed Functional Networks

Neurodevelopmental disorders are increasingly viewed as disorders of distributed brain networks, yet how developmental perturbations generate co-occurring hypo- and hyper-functional network states remains unclear. We show that Syngap1 haploinsufficiency in mice produces opposing cortical activity patterns: sensory-evoked responses exhibit reduced gain, whereas state-linked movement/arousal activity is amplified. Restricting Syngap1 deficiency to developing cortical excitatory neurons reproduces distributed sensory hypofunction but not movement-linked hyperfunction, indicating non-uniform, cell-type-dependent contributions to these patterns. During a postnatal window of circuit assembly, Layer 2/3 intratelencephalic populations across cortical regions occupy distinct maturation states, reflected in separable dendritic architectures and intrinsic excitability. Perturbing Syngap1 reduces this developmental separability through region-dependent, opposite-direction effects on dendritic maturation and inversion of ERK-sensitive control of intrinsic excitability. We propose that coordinated relative maturation of interacting neuronal populations establishes distributed network balance, and that gene-dependent shifts in this coordination produce stable, opposing network states.