Behavioral tagging is a general mechanism of long-term memory formation

In daily life, memories are intertwined events. Little is known about the mechanisms involved in their interactions. Using two hippocampus-dependent (spatial object recognition and contextual fear conditioning) and one hippocampus-independent (conditioned taste aversion) learning tasks, we show that in rats subjected to weak training protocols that induce solely short term memory (STM), long term memory (LTM) is promoted and formed only if training sessions took place in contingence with a novel, but not familiar, experience occurring during a critical time window around training. This process requires newly synthesized proteins induced by novelty and reveals a general mechanism of LTM formation that begins with the setting of a “learning tag” established by a weak training. These findings represent the first comprehensive set of evidences indicating the existence of a behavioral tagging process that in analogy to the synaptic tagging and capture process, need the creation of a transient, protein synthesis-independent, and input specific tag.

[1]  J. Konorski.  Conditioned reflexes and neuron organization. , 1948 .

[2]  F. Attneave,et al.  The Organization of Behavior: A Neuropsychological Theory , 1949 .

[3]  J. Knott.  The organization of behavior: A neuropsychological theory , 1951 .

[4]  James L. McGaugh,et al.  Insular cortex and amygdala lesions differentially affect acquisition on inhibitory avoidance and conditioned taste aversion , 1991, Brain Research.

[5]  M. Fanselow,et al.  Modality-specific retrograde amnesia of fear. , 1992, Science.

[6]  Masatoshi Hagiwara,et al.  Phosphorylated CREB binds specifically to the nuclear protein CBP , 1993, Nature.

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

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

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

[10]  J. Sweatt,et al.  Toward a molecular explanation for long-term potentiation. , 1999, Learning & memory.

[11]  Sweatt Jd,et al.  Toward a molecular explanation for long-term potentiation. , 1999 .

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

[13]  Y. Dudai,et al.  Memory Extinction, Learning Anew, and Learning the New: Dissociations in the Molecular Machinery of Learning in Cortex , 2001, Science.

[14]  M. Miranda,et al.  Glutamatergic activity in the amygdala signals visceral input during taste memory formation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Mumby,et al.  Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts. , 2002, Learning & memory.

[16]  I. Izquierdo,et al.  BDNF–triggered events in the rat hippocampus are required for both short‐ and long‐term memory formation , 2002, Hippocampus.

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

[18]  Thomas Straube,et al.  Requirement of beta-adrenergic receptor activation and protein synthesis for LTP-reinforcement by novelty in rat dentate gyrus. , 2003, The Journal of physiology.

[19]  J. Medina,et al.  ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons. , 2004, Learning & memory.

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

[21]  F. Bermúdez-Rattoni.  Molecular mechanisms of taste-recognition memory , 2004, Nature Reviews Neuroscience.

[22]  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.

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

[24]  T. Sacktor,et al.  Synaptic Tagging and Cross-Tagging: The Role of Protein Kinase Mζ in Maintaining Long-Term Potentiation But Not Long-Term Depression , 2005, The Journal of Neuroscience.

[25]  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.

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

[27]  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.

[28]  Martín Cammarota,et al.  Different molecular cascades in different sites of the brain control memory consolidation , 2006, Trends in Neurosciences.

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

[30]  D. Moncada,et al.  Induction of Long-Term Memory by Exposure to Novelty Requires Protein Synthesis: Evidence for a Behavioral Tagging , 2007, The Journal of Neuroscience.

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

[32]  I. Izquierdo,et al.  BDNF is essential to promote persistence of long-term memory storage , 2008, Proceedings of the National Academy of Sciences.

[33]  J. M. Alarcon,et al.  Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited 10 years later , 2008, Neuroscience & Biobehavioral Reviews.

[34]  M. Escobar,et al.  BDNF reverses the CTA memory deficits produced by inhibition of protein synthesis , 2008, Neurobiology of Learning and Memory.

[35]  Haruo Kasai,et al.  Protein Synthesis and Neurotrophin-Dependent Structural Plasticity of Single Dendritic Spines , 2008, Science.

[36]  Mark Mayford,et al.  Spine-Type-Specific Recruitment of Newly Synthesized AMPA Receptors with Learning , 2008, Science.

[37]  Nahum Sonenberg,et al.  Translational control of gene expression : a molecular switch for memory storage , 2009 .

[38]  D. Moncada,et al.  PKMzeta inactivation induces spatial familiarity. , 2008, Learning & memory.

[39]  J. Frey,et al.  'Synaptic tagging' and 'cross-tagging' and related associative reinforcement processes of functional plasticity as the cellular basis for memory formation. , 2008, Progress in brain research.

[40]  K. Christian,et al.  BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory? , 2008, Neurobiology of Learning and Memory.