Requirement of NMDA receptor reactivation for consolidation and storage of nondeclarative taste memory revealed by inducible NR1 knockout.
We employed an inducible, reversible and region-specific gene knockout technique to investigate the requirements for cortical NMDA receptors (NMDAR) during the various stages (acquisition, consolidation and storage, and retrieval) of nondeclarative, hippocampal-independent memory in mice using a conditioned taste aversion memory paradigm. Here we show that temporary knockout of the cortical NMDAR during either the learning or postlearning consolidation stage, but not during the retrieval stage, causes severe performance deficits in the 1-month taste memory retention tests. More importantly, we found that the consolidation and storage of the long-term nondeclarative taste memories requires cortical NMDAR reactivation. Thus, the dynamic engagement of the NMDAR during the postlearning stage leads us to postulate that NMDAR reactivation-mediated synaptic re-entry reinforcement is crucial for overcoming the destabilizing effects intrinsic to synaptic protein turnover and for achieving consolidation and storage of nondeclarative memories in the brain.
Cui
Zhenzhong
Z
Center for Systems Neurobiology, Department of Pharmacology, Boston University, Boston, MA 02118, USA.
Lindl
Kathryn A
KA
Mei
Bing
B
Zhang
Shuqing
S
Tsien
Joe Z
JZ
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology*; D003213:Conditioning, Psychological; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D019426:Integrases / Q000235:genetics; D018021:Lithium Chloride / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012439:Saccharin / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D016326:Extracellular Matrix Proteins; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D013549:Sweetening Agents; D049452:Green Fluorescent Proteins; C077112:Lox protein, mouse; D008249:Protein-Lysine 6-Oxidase; C045073:Cre recombinase; D019426:Integrases; D012439:Saccharin; D018021:Lithium Chloride