A cardinal feature of human brain development is that sensory, cognitive, and emotional experiences shape synapses and neural-circuit development. Neuronal activity triggers changes at the synapse, altering the composition, shape and strength of the synapse. These neuronal activity-dependent modifications are necessary for learning and memory and various behavioural responses, particularly during development. Several studies have shown that these features are disrupted in Intellectual Disability (ID) and Autism Spectrum Disorder (ASD), which affects ~3-4% of the population in the world. Mutations that cause ID and ASD are increasingly found in genes that encode proteins that regulate synaptic function and structure. De novo heterozygous (het) mutations in the gene that encodes for synaptic RASGAP, SYNGAP1, has been shown to cause ID and increase the risk for developing ASD in young children. It has been demonstrated that, in Syngap1 heterozygous mutant (Het) mice, the net effect of a heterozygous mutation in Syngap1 was to unleash dendritic spine synapse in the neonatal hippocampus during development, which drives excitatory/inhibitory (E/I) imbalance, seizures and various behavioural deficits. This early dendritic synaptic spine maturation is also linked to the altered duration of the critical period of plasticity that leads to life-long cognitive and social deficits.
Image 1: Whole-cell patch-clamp of a mouse CA1 pyramidal cell
Image 2: YFP expressing mouse brain
Image 3: Neuron from a primary neuronal culture
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