Background: Autism Spectrum Disorder (ASD) has been linked to mutations in genes coding for proteins that function at the synapse—the location where neurons transmit electrical and chemical signals. The gene SYNGAP1 encodes one such synaptic protein. The mechanism through which synaptic dysfunction affects neural circuits and behavior is not well understood.

What’s new: Early synapse maturation can lead to irreversible cognitive and behavioral deficits in mice, according to a recent study published in the journal Cell. Researchers used a mouse model lacking the SYNGAP1 gene to investigate the role of SYNGAP1 in synapse development and, by extension, the role of synapse development in cognitive and behavior deficits. The authors reported that synapses associated with small protrusions on the receiving branches of the neuron, known as dendritic spines, mature at a faster rate in the postnatal mouse model lacking SYNGAP1. The acceleration of synapse maturation resulted in increased neural excitability and behavioral abnormalities. The researchers identified a critical developmental window, as elminating SYNGAP1 outside the window minimally impacted synapse function, and reversing the mutation in adulthood had no effect.

Why it’s important: Excitatory/Inhibitory imbalance in the brain is a striking neurophysiological feature of many neurodevelopmental disorders like ASD and Intellectual Disability (ID). This study suggests that mutations in genes that encode synaptic proteins may affect critical windows of cortical development by altering the rate of synapse development, leading to increased neural excitability and cognitive dysfunction. Further studies are needed to identify the effects of synaptic disruptions on neuronal circuit organization in the brain.

Brain Biology

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