Reduced Slc1a1 expression is associated with neuroinflammation and impaired sensorimotor gating and cognitive performance in mice: implications for schizophrenia

We characterized the in vivo and in vitro consequences of reduced expression of Slc1a1 in mice. Heterozygous (HET) Slc1a1+/- mice, which model the hemi-deletion we found in human subjects with schizophrenia, were examined in a series of behavioral, anatomical and biochemical assays. Knockout (KO) mice were also included in the behavioral studies for comparative purposes. Both HET and KO mice exhibited evidence of increased anxiety-like behavior, impaired working memory, decreased exploratory activity and impaired sensorimotor gating, but no changes in overall locomotor activity compared to wildtype (WT) mice. The magnitude of changes was approximately equivalent in the HET and KO mice suggesting a dominant effect of the haploinsufficiency. Whole transcriptome RNA-Seq analysis detected expression changes of genes and pathways involved in cytokine signaling and synaptic functions in both brain and blood of the HET mice compared to WT mice. mRNA profiles of the whole brain and whole blood of young adult wild type (WT) Slc1a1 +/+ and heterozygous (HET) Slc1a1 +/- mice were generated by stranded RNA-seq, with n = 5 per genotype per tissue, using an Illumina NextSeq500.