[Abstract Title]. - Society for Neuroscience

pathology, we compared the expression levels of GLS1, GluR2, the NMDA receptor subunit
NR1 and CamKII (a gene involved in long-term plasticity pathways) in the HIPP of GLS1 hets
and NR1 hypomorphic mice, which have 10% of normal NR1 expression levels and a SZ-like
behavioral phenotype (Mohn et al., Cell 1999). GLS1 hets displayed a reduction in GLS1, GluR2
and CamKII, but not NR1. In contrast, NR1 hypomorphs displayed a reduction in NR1
expression only. These distinctly different gene expression profiles indicate that a reduction in
GLS1, and in presynaptic GLU, does not mimic the gene expression effects of reduced NMDA
receptor expression, consistent with our previous findings showing that a reduction in GLS1
leads to an array of functional, behavioral and neurochemical phenotypes that are the inverse of
what is typically observed in SZ. In line with current thinking that SZ is related to excessive
GLU signaling via AMPA receptors, possibly the beneficial effects of reducing GLS1 expression
are mediated through the associated reduction in GluR2.
Disclosures: I. Gaisler-Salomon , None; Y. Wang, None; S.M. McKinney, None; A.J.
Ramsey, None; E.L. Sibille, None; S. Rayport, None.
Poster
254. Schizophrenia: Mutant Animal Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 254.3/X20
Topic: C.15.d. Schizophrenia: Mutant animal models
Support: MH051290 .
P50 MH060450
Title: Relationship between NMDA receptor function and GABAergic neuropathology in serine
racemase and glycine transporter I mutant mice
Authors: M. A. BENNEYWORTH, K. SUZUKI, *A. C. BASU, J. T. COYLE;
Psychiatry - McLean Hosp, Harvard Med. Sch., Belmont, MA
Abstract: Reduction in presynaptic markers for parvalbumin(PV)-positive GABAergic
interneurons in the cortex is the most highly replicated postmortem neurochemical finding in
schizophrenia. Meanwhile, mounting evidence from genetic and pharmacologic studies
implicates hypofunction of NMDA receptor-mediated glutamatergic signaling as a critical
component of the pathophysiology of schizophrenia. A potential relationship between these
findings exists in the context of the circuitry of the cortex, where PV-positive GABAergic
interneurons provide feedback inhibition to the cortical pyramidal cells. We asked whether a