NR2B-dependent plasticity of adult-born granule cells is necessary for context discrimination.
Adult-generated granule cells (GCs) in the dentate gyrus (DG) exhibit a period of heightened plasticity 4-6 weeks postmitosis. However, the functional contribution of this critical window of plasticity to hippocampal neurogenesis and behavior remains unknown. Here, we show that deletion of NR2B-containing NMDA receptors from adult-born GCs impairs a neurogenesis-dependent form of LTP in the DG and reduces dendritic complexity of adult-born GCs, but does not impact their survival. Mice in which the NR2B-containing NMDA receptor was deleted from adult-born GCs did not differ from controls in baseline anxiety-like behavior or discrimination of very different contexts, but were impaired in discrimination of highly similar contexts. These results indicate that NR2B-dependent plasticity of adult-born GCs is necessary for fine contextual discrimination and is consistent with their proposed role in pattern separation.
Department of Neuroscience, Columbia University, New York, New York 10032, USA.
Mazen A
MA
Kheirbek
Lindsay
L
Tannenholz
René
R
Hen
D000818:Animals; D001007:Anxiety / Q000523:psychology; D002470:Cell Survival; D003213:Conditioning, Psychological; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D004192:Discrimination, Psychological / Q000502:physiology*; D005239:Fear / Q000523:psychology; D005247:Feeding Behavior / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009415:Nerve Net / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D055495:Neurogenesis; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology; D013550:Swimming / Q000523:psychology
D007381:Intermediate Filament Proteins; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016194:Receptors, N-Methyl-D-Aspartate