Glutaminase-deficient @entity19 (GLS1 hets), with reduced @entity2227 recycling, have a focal reduction in hippocampal activity, mainly in @entity4778 , and manifest behavioral and neurochemical phenotypes suggestive of @entity161 resilience. To address the basis for the @entity131 , we examined synaptic plastic mechanisms and @entity2227 receptor expression. Although baseline synaptic strength was unaffected in Schaffer collateral inputs to @entity4778 , we found that long-term potentiation was attenuated. In @entity164 ( @entity164 ) @entity19 , GLS1 gene expression was highest in the hippocampus and cortex, where it was reduced by about 50% in GLS1 hets. In other brain regions with lower @entity164 GLS1 gene expression, there were no genotypic reductions. In adult GLS1 hets, @entity143 receptor @entity13429 subunit gene expression was reduced, but not @entity140 receptor @entity9446 subunit gene expression. In contrast, juvenile GLS1 hets showed no reductions in @entity13429 gene expression. In concert with this, adult GLS1 hets showed a deficit in hippocampal-dependent contextual fear conditioning, whereas juvenile GLS1 hets did not. These alterations in glutamatergic synaptic function may partly explain the @entity131 seen in the GLS1 hets. The maturity-onset reduction in @entity13429 gene expression and in contextual learning supports the premise that glutaminase inhibition in adulthood should prove therapeutic in @entity161 .

Synaptic underpinnings of altered hippocampal function in glutaminase-deficient XXXX during maturation.

@entity131 :: ('MESH:D001930', 'Disease') :: ['hippocampal hypoactivity'] @entity2227 :: ('CHEBI:29987', 'Chemical') :: ['glutamate'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity13429 :: ('14810(Tax:10090)', 'Gene') :: ['NR1'] @entity4778 :: ('12346(Tax:10090)', 'Gene') :: ['CA1'] @entity9446 :: ('14799(Tax:10090)', 'Gene') :: ['GluR1'] @entity161 :: ('MESH:D012559', 'Disease') :: ['schizophrenia'] @entity164 :: ('MESH:D017827', 'Disease') :: ['WT', 'wild-type'] @entity143 :: ('CHEBI:6121', 'Chemical') :: ['NMDA'] @entity140 :: ('MESH:D018350', 'Chemical') :: ['AMPA']
@entity19 :: (10090,Species) :: ['mice']
