Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analysis of Variance
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Animals
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Avoidance Learning / drug effects
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Avoidance Learning / physiology*
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Behavior, Animal / physiology
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Cerebral Cortex / anatomy & histology
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Cerebral Cortex / physiology*
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Conditioning, Psychological
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Extracellular Matrix Proteins / genetics
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Extracellular Matrix Proteins / metabolism
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Gene Expression Regulation / physiology
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Green Fluorescent Proteins / biosynthesis
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Integrases / genetics
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Lithium Chloride / pharmacology
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Memory / drug effects
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Memory / physiology*
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Mice
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Mice, Transgenic
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Protein-Lysine 6-Oxidase / genetics
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Protein-Lysine 6-Oxidase / metabolism
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Receptors, N-Methyl-D-Aspartate / deficiency
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Receptors, N-Methyl-D-Aspartate / genetics
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Receptors, N-Methyl-D-Aspartate / physiology*
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Saccharin / pharmacology
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Sweetening Agents / pharmacology
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Taste / drug effects
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Taste / physiology*
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Time Factors
Substances
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Extracellular Matrix Proteins
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NR1 NMDA receptor
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Receptors, N-Methyl-D-Aspartate
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Sweetening Agents
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Green Fluorescent Proteins
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Lox protein, mouse
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Protein-Lysine 6-Oxidase
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Cre recombinase
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Integrases
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Saccharin
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Lithium Chloride