期刊
NEUROBIOLOGY OF LEARNING AND MEMORY
卷 136, 期 -, 页码 244-250出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nlm.2016.09.006
关键词
NMDA receptor; Glycine modulatory site; D-Serine; Trace conditioning; Contextual conditioning
资金
- NIH (United States) Grants [RO1 MH051290, P50 MH060450]
- NARSAD/Shine Initiative Young Investigator Award
- College of the Holy Cross
We have used mutant mice to probe the roles of the endogenous co-agonists of the NMDA receptor (NMDAR), D-serine and glycine, in fear learning and memory. Serine racemase knockout (SR-/-) mice have less than 15% of wild type forebrain levels of D-serine, whereas glycine transporter 1 heterozygous knockout (GlyT1+/-) mice have elevated synaptic glycine. While cued fear was normal in both delay and trace conditioned mice of both mutant genotypes, contextual fear was affected in trace conditioned subjects: SR-/-mice showed decreased contextual freezing, whereas G1yT1+/- mice showed elevated contextual freezing. These results indicate that endogenous co-agonists of the NMDAR modulate the conditioning of contextual fear responses, particularly in trace conditioning. They further suggest that endogenous glycine can compensate for the D-serine deficiency in cued and contextual fear following delay conditioning. (C) 2016 Elsevier Inc. All rights reserved.
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