[Abstract Title]. - Society for Neuroscience

Poster
254. Schizophrenia: Mutant Animal Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 254.2/X19
Topic: C.15.d. Schizophrenia: Mutant animal models
Support: T32 DA016224 (IGS)
K02 DA000356 (SR)
P50 MH066171 (SR)
Title: Differential expression of AMPA and NMDA receptors in the hippocampus of
Glutaminase-deficient mice
Authors: *I. GAISLER-SALOMON 1,2 , Y. WANG 1,2 , S. M. MCKINNEY 1,2 , A. J. RAMSEY 3 ,
E. L. SIBILLE 4 , S. RAYPORT 1,2 ;
1 Columbia Univ., NYC, NY; 2 Mol. Therapeut., New York State Psychiatric Inst., New York
City, NY; 3 Cell Biol., Duke Univ. Med. Ctr., Durham, NC; 4 Psychiatry, Univ. of Pittsburgh,
Pittsburgh, PA
Abstract: Glutamate (GLU) signaling in the hippocampus (HIPP) is fundamental to learning and
memory; its disruption has been linked to schizophrenia (SZ) and several other disorders. We
showed previously that glutaminase-deficient mice (GLS1 hets), with a presynaptic defect in
GLU recycling, have reduced glutamate levels in several brain regions, but a focal reduction in
HIPP activity, measured using in-vivo imaging and electrophysiological techniques, and a
selective deficit in HIPP-dependent contextual learning (Gaisler-Salomon et al., SFN 2007).
Extending this work, we asked: (1) Are other genes involved in glutamine-GLU recycling
pathway, or related metabolic pathways, affected in the HIPP of GLS1 hets? (2) Is NMDA and
AMPA receptor expression altered in GLS1 hets? (3) How are learning and memory-related
genes affected? Using Affymetrix gene chips, we found that (1) other than GLS1, which was
downregulated by about 50%, enzymes involved in glutamine-GLU recycling or related
metabolic pathways were unaffected. (2) The GluR2 receptor subunit of the AMPA receptor was
downregulated by 40%, while NMDA receptor expression was unaffected. RT-PCR performed
on HIPP and frontal cortex samples confirmed the HIPP-specific reduction in GluR2 expression
(3) Although no single molecule implicated in learning-related cascades was drastically affected,
Ingenuity Pathway analysis showed dysregulation of the long-term plasticity pathway. This was
confirmed using RT-PCR, which also showed that the effect was specific to the HIPP. In order to
examine the relevance of changes in gene expression observed in GLS1 hets to SZ-related