Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders


NE-Munroe-Meyer Institute of Genetics & Rehabilitation, UCEDD/LEND
Program TypeUCEDD Fiscal Year 2016
Date of Publication11/2015 Author(s)Padmashri Ragunathan
Type of Material
Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders
Brain Behav Immun
Publisher 0
Brief Description Both genetic and environmental factors are thought to contribute to neurodevelopmental and neuropsychiatric disorders with maternal immune activation (MIA) being a risk factor for both autism spectrum disorders and schizophrenia. Although MIA mouse offspring exhibit behavioral impairments, the synaptic alterations in vivo that mediate these behaviors are not known. Here we employed in vivo multiphoton imaging to determine that in the cortex of young MIA offspring there is a reduction in number and turnover rates of dendritic spines, sites of majority of excitatory synaptic inputs. Significantly, spine impairments persisted into adulthood and correlated with increased repetitive behavior, an ASD relevant behavioral phenotype. Structural analysis of synaptic inputs revealed a reorganization of presynaptic inputs with a larger proportion of spines being contacted by both excitatory and inhibitory presynaptic terminals. These structural impairments were accompanied by altered excitatory an
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