Haploinsufficiency of SYNGAP1 (synaptic RAS GTPase activating protein 1) in humans can lead to intellectual disability and epilepsy, and Syngap1+/− mice exhibit impaired cognition. Here, in mice, heterozygous knockout of Syngap1 in developing forebrain pyramidal neurons, but not in GABAergic neurons, was sufficient to replicate the Syngap1+/− mouse phenotype. Reduction of SYNGAP1 levels in adult mice had no effect on cognition or pyramidal neuron excitability, indicating that the cognitive impairment in Syngap1+/− mice is due to altered development of forebrain excitatory neurons.
References
Ozkan, E. D. et al. Reduced cognition in Syngap1 mutants is caused by isolated damage within developing forebrain excitatory neurons. Neuron 82, 1317–1333 (2014)
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Bray, N. Mind the SYNGAP. Nat Rev Neurosci 15, 495 (2014). https://doi.org/10.1038/nrn3793
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DOI: https://doi.org/10.1038/nrn3793