Reduced cognition in Syngap1 mutants is caused by isolated damage within developing forebrain excitatory neurons.

ABSTRACT: Syngap1 haploinsufficiency is a common cause of sporadic intellectual disability. Syngap1 mutations disrupt developing pyramidal neurons, although it remains unclear if this process contributes to cognitive abnormalities. Here, we found that haploinsufficiency restricted to forebrain glutamatergic neurons was sufficient to disrupt cognition and removing mutations from this population prevented cognitive abnormalities. In contrast, manipulating Syngap1 function in GABAergic neurons had no effect on cognition, excitability, or neurotransmission, highlighting the specificity of Syngap1 mutations within forebrain excitatory neurons. Interestingly, cognitive abnormalities were reliably predicted by the emergence of enhanced excitatory synaptic function in mature superficial cortical pyramidal c

SUBMITTER: Ozkan ED 

PROVIDER: S-EPMC4104574 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature