title: Endogenous co-agonists of the NMDA receptor modulate contextual fear in trace conditioning.
abstract: 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 GlyT1+/- 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.
authors.affiliation: Laboratory for Molecular and Psychiatric Neuroscience, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA; Department of Psychology, College of the Holy Cross, Worcester, MA 01610, USA. Electronic address: abasu@holycross.edu.
authors.forename: Alo C
authors.initials: AC
authors.lastname: Basu
authors.affiliation: Laboratory for Molecular and Psychiatric Neuroscience, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Puhl
authors.affiliation: Laboratory for Molecular and Psychiatric Neuroscience, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Coyle
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D003463:Cues; D005239:Fear / Q000502:physiology*; D005998:Glycine / Q000172:deficiency / Q000502:physiology*; D050487:Glycine Plasma Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019998:Racemases and Epimerases / Q000172:deficiency / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012694:Serine / Q000172:deficiency / Q000502:physiology*; D000099300:Serine Racemase
chemical_list: D005998:Glycine; D050487:Glycine Plasma Membrane Transport Proteins; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase; C493267:Slc6a9 protein, mouse
keywords: Contextual conditioning; D-Serine; Glycine modulatory site; NMDA receptor; Trace conditioning