Mutations that cause intellectual disability (ID) and autism spectrum disorder 
(ASD) are commonly found in genes that encode for synaptic proteins. However, it 
remains unclear how mutations that disrupt synapse function impact intellectual 
ability. In the SYNGAP1 mouse model of ID/ASD, we found that dendritic spine 
synapses develop prematurely during the early postnatal period. Premature spine 
maturation dramatically enhanced excitability in the developing hippocampus, 
which corresponded with the emergence of behavioral abnormalities. Inducing 
SYNGAP1 mutations after critical developmental windows closed had minimal impact 
on spine synapse function, whereas repairing these pathogenic mutations in 
adulthood did not improve behavior and cognition. These data demonstrate that 
SynGAP protein acts as a critical developmental repressor of neural excitability 
that promotes the development of life-long cognitive abilities. We propose that 
the pace of dendritic spine synapse maturation in early life is a critical 
determinant of normal intellectual development.