Figure 1.

Constitutive NMDA-receptor hypofunction causes a selective disruption of parvalbumin-expressing (PV+), fast-spiking interneurons (FSI). (a) Immunoreactivity for FSI was significantly reduced in NR1^neo−/− mice. (b) Protein expression for markers of GABA interneuron populations was assessed by western blot. Calbindin and calretinin are markers for nonfast-spiking interneurons, whereas GAD65 and GAD67 are expressed in all GABAergic interneurons. PV expression was significantly reduced in NR1^neo−/− mice, whereas other proteins were unaffected. (c) No group differences were observed following in situ hybridization for PV mRNA, indicating that FSI were present, but disrupted, in NR1^neo−/− mice. (d) Expression of postsynaptic GABA_A- and GABA_B-receptor subunits was measured by quantitative PCR (qPCR). The GABA_A-receptor alpha-2 subunit was significantly upregulated in NR1^neo−/− mice as seen in schizophrenia,⁵⁵ whereas other subunits were unaffected. Figures show mean +/− s.e.m., ^*P<0.05, ^**P<0.01, ^***P<0.001.