Induction of Long-Term Memory by Exposure to Novelty Requires Protein Synthesis: Evidence for a Behavioral Tagging

A behavioral analog of the synaptic tagging and capture process, a key property of synaptic plasticity, has been predicted recently. Here, we demonstrate that weak inhibitory avoidance training, which induces short- but not long-term memory (LTM), can be consolidated into LTM by an exploration to a novel, but not a familiar, environment occurring close in time to the training session. This memory-promoting effect caused by novelty depends on activation of dopamine D1/D5 receptors and requires newly synthesized proteins in the dorsal hippocampus. Thus, our results indicate the existence of a behavioral tagging process in which the exploration to a novel environment provides the plasticity-related proteins to stabilize the inhibitory avoidance memory trace.

[1]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[2]  L. Swanson The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[3]  U. Frey,et al.  Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices , 1990, Brain Research.

[4]  U. Frey,et al.  The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro , 1991, Neuroscience Letters.

[5]  R. Knight Contribution of human hippocampal region to novelty detection , 1996, Nature.

[6]  U. Frey,et al.  Synaptic tagging and long-term potentiation , 1997, Nature.

[7]  I Izquierdo,et al.  Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[8]  R. Bernabeu,et al.  Involvement of hippocampal D1/D5 receptor-cAMP signaling pathways in a late memory consolidation phase of an aversively-motivated task in rats , 1997 .

[9]  K Lehnertz,et al.  Verbal novelty detection within the human hippocampus proper. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Michael J. Rowan,et al.  Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus , 1998, Nature.

[11]  U. Frey,et al.  Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation , 1998, Trends in Neurosciences.

[12]  U. Frey,et al.  Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP , 1998, Neuropharmacology.

[13]  I Izquierdo,et al.  Role of hippocampal signaling pathways in long-term memory formation of a nonassociative learning task in the rat. , 2000, Learning & memory.

[14]  S. J. Martin,et al.  Synaptic plasticity and memory: an evaluation of the hypothesis. , 2000, Annual review of neuroscience.

[15]  C. Alberini,et al.  Fornix-Dependent Induction of Hippocampal CCAAT Enhancer-Binding Protein β and δ Co-Localizes with Phosphorylated cAMP Response Element-Binding Protein and Accompanies Long-Term Memory Consolidation , 2001, The Journal of Neuroscience.

[16]  K. Martin,et al.  Synaptic tagging — who's it? , 2002, Nature Reviews Neuroscience.

[17]  E. Baldi,et al.  Time‐dependent inhibition of hippocampal LTP in vitro following contextual fear conditioning in the rat , 2002, The European journal of neuroscience.

[18]  I. Izquierdo,et al.  Two Time Periods of Hippocampal mRNA Synthesis Are Required for Memory Consolidation of Fear-Motivated Learning , 2002, The Journal of Neuroscience.

[19]  R. Prado-Alcalá,et al.  Effects of Lesions of Hippocampal Fields CA1 and CA3 on Acquisition of Inhibitory Avoidance , 2002, Neuropsychobiology.

[20]  J. Frey,et al.  Bidirectional modulation of long-term potentiation by novelty-exploration in rat dentate gyrus , 2003, Neuroscience Letters.

[21]  W. K. Cullen,et al.  Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty , 2003, Nature Neuroscience.

[22]  I. Izquierdo,et al.  Exposure to novelty enhances retrieval of very remote memory in rats , 2003, Neurobiology of Learning and Memory.

[23]  Thomas Straube,et al.  Requirement of β‐adrenergic receptor activation and protein synthesis for LTP‐reinforcement by novelty in rat dentate gyrus , 2003 .

[24]  I. Izquierdo,et al.  Inhibition of mRNA and Protein Synthesis in the CA1 Region of the Dorsal Hippocampus Blocks Reinstallment of an Extinguished Conditioned Fear Response , 2003, The Journal of Neuroscience.

[25]  C. Ferrari,et al.  Learning modulation by endogenous hippocampal IL‐1: Blockade of endogenous IL‐1 facilitates memory formation , 2004, Hippocampus.

[26]  S. Sajikumar,et al.  Resetting of ‘synaptic tags’ is time- and activity-dependent in rat hippocampal CA1in vitro , 2004, Neuroscience.

[27]  F. L. Jones,et al.  Novel Environments Enhance the Induction and Maintenance of Long-Term Potentiation in the Dentate Gyrus , 2004, The Journal of Neuroscience.

[28]  R. Morris,et al.  Heterosynaptic co-activation of glutamatergic and dopaminergic afferents is required to induce persistent long-term potentiation , 2004, Neuropharmacology.

[29]  E. Kandel,et al.  Increased Attention to Spatial Context Increases Both Place Field Stability and Spatial Memory , 2004, Neuron.

[30]  Jennie Z. Young,et al.  Homosynaptic and Heterosynaptic Inhibition of Synaptic Tagging and Capture of Long-Term Potentiation by Previous Synaptic Activity , 2005, The Journal of Neuroscience.

[31]  J. Lisman,et al.  The Hippocampal-VTA Loop: Controlling the Entry of Information into Long-Term Memory , 2005, Neuron.

[32]  J. Frey,et al.  Reinforcement of rat hippocampal LTP by holeboard training. , 2005, Learning & memory.

[33]  W. B. Smith,et al.  Dopaminergic Stimulation of Local Protein Synthesis Enhances Surface Expression of GluR1 and Synaptic Transmission in Hippocampal Neurons , 2005, Neuron.

[34]  T. Abel,et al.  Metaplasticity of the late‐phase of long‐term potentiation: a critical role for protein kinase A in synaptic tagging , 2006, The European journal of neuroscience.

[35]  S. Tonegawa,et al.  A clustered plasticity model of long-term memory engrams , 2006, Nature Reviews Neuroscience.

[36]  D. Moncada,et al.  Phosphorylation state of CREB in the rat hippocampus: A molecular switch between spatial novelty and spatial familiarity? , 2006, Neurobiology of Learning and Memory.

[37]  E. Kandel,et al.  Age-related enhancement of a protein synthesis-dependent late phase of LTP induced by low frequency paired-pulse stimulation in hippocampus. , 2006, Learning & memory.

[38]  Agnès Gruart,et al.  Involvement of the CA3–CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice , 2006, The Journal of Neuroscience.

[39]  Jonathan R. Whitlock,et al.  Learning Induces Long-Term Potentiation in the Hippocampus , 2006, Science.

[40]  R. Morris,et al.  Elements of a neurobiological theory of hippocampal function: the role of synaptic plasticity, synaptic tagging and schemas , 2006, The European journal of neuroscience.

[41]  J. Frey,et al.  The late maintenance of hippocampal LTP: Requirements, phases, ‘synaptic tagging’, ‘late-associativity’ and implications , 2007, Neuropharmacology.

[42]  I. Izquierdo,et al.  Persistence of Long-Term Memory Storage Requires a Late Protein Synthesis- and BDNF- Dependent Phase in the Hippocampus , 2007, Neuron.