Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice

• Published in: Nature neuroscience Vol. 3; no. 3; pp. 238 - 244
• Main Authors: Kyin, Maureen, Tsien, Joe Z, Rampon, Claire, Tang, Ya-Ping, Goodhouse, Joe, Shimizu, Eiji
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.03.2000
• Subjects: Animal memory; Animals; Conditioning (Psychology) - physiology; Cues; Dendrites - physiology; Dendrites - ultrastructure; Diagnosis; Electron microscopy; Electroshock; Enrichment; Exploratory Behavior - physiology; Fear - physiology; Female; Food Preferences - physiology; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Ion channels; Laboratory animals; Long-Term Potentiation - physiology; Male; Memory; Memory - physiology; Memory Disorders - genetics; Memory Disorders - physiopathology; Memory, Disorders of; Mice; Mice, Knockout; Microscopy; N-Methyl-D-aspartic acid receptors; Neuroplasticity; Object recognition; Olfactory discrimination; Olfactory discrimination learning; Pattern recognition; Pattern Recognition, Visual - physiology; Physiological aspects; Pyramidal Cells - cytology; Pyramidal Cells - growth & development; Pyramidal Cells - physiology; Pyramidal Cells - ultrastructure; Receptors; Receptors, N-Methyl-D-Aspartate - deficiency; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - physiology; Retention; Risk factors; Rodents; Smell - physiology; Space Perception - physiology; Synapses - physiology; Synapses - ultrastructure; Synaptic density; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/72945

We produced CA1-specific NMDA receptor 1 subunit-knockout (CA1-KO) mice to determine the NMDA receptor dependence of nonspatial memory formation and of experience-induced structural plasticity in the CA1 region. CA1-KO mice were profoundly impaired in object recognition, olfactory discrimination and contextual fear memories. Surprisingly, these deficits could be rescued by enriching experience. Using stereological electron microscopy, we found that enrichment induced an increase of the synapse density in the CA1 region in knockouts as well as control littermates. Therefore, our data indicate that CA1 NMDA receptor activity is critical in hippocampus-dependent nonspatial memory, but is not essential for experience-induced synaptic structural changes.