Prescient Synapses: Gating Future Neuronal Consciousness Through Synaptic Tagging and Metaplasticity

Restriction of synaptic plasticity to time frames dictated by fast synaptic transmission would yield neuronal networks incapable of encoding qualitatively rich memories. The ability to associate and encode temporally disparate aspects of a memory confers significant survival advantages. The temporal spread of everyday experiences necessitates broad time windows for synaptic encoding of multiple related events. By extending the time frame in which events can be associated at a synaptic level, and biasing synapses towards a plasticity-conducive state, synaptic tagging and metaplasticity provide potent mechanisms for enhancing memory quality in the brain. Tagging and metaplasticity serve as gateways for augmenting neuronal consciousness. Priming of future synaptic plasticity can enhance neuronal detection, encoding, and association of salient future events, and it can facilitate storage of detailed memories. We review key intracellular signalling mechanisms that initiate lasting changes in the ability of synapses to undergo metaplasticity, along with leading candidate synaptic tags that facilitate metaplasticity. We also speculate on how these phenomena bolster neuronal consciousness to sculpt the brain’s capacity to dynamically encode and store information.

[1]  T. Sacktor,et al.  Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[2]  N. Lemon,et al.  Beta-adrenergic receptor activation during distinct patterns of stimulation critically modulates the PKA-dependence of LTP in the mouse hippocampus. , 2008, Learning & memory (Cold Spring Harbor, N.Y.).

[3]  Masahiko Watanabe,et al.  SK2 channel plasticity contributes to LTP at Schaffer collateral–CA1 synapses , 2008, Nature Neuroscience.

[4]  John Lisman,et al.  Role of the CaMKII/NMDA Receptor Complex in the Maintenance of Synaptic Strength , 2011, The Journal of Neuroscience.

[5]  Jian Wang,et al.  CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP , 1995, Cell.

[6]  Steven A. Connor,et al.  Viagra for your synapses: Enhancement of hippocampal long-term potentiation by activation of beta-adrenergic receptors. , 2010, Cellular signalling.

[7]  T. Abel,et al.  Regulation of hippocampus-dependent memory by cyclic AMP-dependent protein kinase. , 2008, Progress in brain research.

[8]  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.

[9]  F. Ballarini,et al.  Identification of transmitter systems and learning tag molecules involved in behavioral tagging during memory formation , 2011, Proceedings of the National Academy of Sciences.

[10]  Roberto Malinow,et al.  AMPA Receptor Incorporation into Synapses during LTP: The Role of Lateral Movement and Exocytosis , 2009, Neuron.

[11]  T. Soderling,et al.  Extrasynaptic Membrane Trafficking Regulated by GluR1 Serine 845 Phosphorylation Primes AMPA Receptors for Long-term Potentiation* , 2006, Journal of Biological Chemistry.

[12]  W. Abraham.  Metaplasticity: tuning synapses and networks for plasticity , 2008, Nature Reviews Neuroscience.

[13]  W. Scoville,et al.  LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS , 1957, Journal of neurology, neurosurgery, and psychiatry.

[14]  Tingyu Li,et al.  Mechanisms of Hippocampal Long-Term Depression Are Required for Memory Enhancement by Novelty Exploration , 2012, The Journal of Neuroscience.

[15]  Karl Peter Giese,et al.  Inhibitory Autophosphorylation of CaMKII Controls PSD Association, Plasticity, and Learning , 2002, Neuron.

[16]  M. Bear,et al.  Metaplasticity: the plasticity of synaptic plasticity , 1996, Trends in Neurosciences.

[17]  T. Bliss,et al.  The Hippocampus Book , 2006 .

[18]  Michael Davis,et al.  A Metaplasticity-Like Mechanism Supports the Selection of Fear Memories: Role of Protein Kinase A in the Amygdala , 2012, The Journal of Neuroscience.

[19]  Eric R Kandel,et al.  Capture of the Late Phase of Long-Term Potentiation within and across the Apical and Basilar Dendritic Compartments of CA1 Pyramidal Neurons: Synaptic Tagging Is Compartment Restricted , 2006, The Journal of Neuroscience.

[20]  Samuel Schacher,et al.  Mechanisms for Generating the Autonomous cAMP-Dependent Protein Kinase Required for Long-Term Facilitation in Aplysia , 1999, Neuron.

[21]  T. Sacktor.  How does PKMζ maintain long-term memory? , 2011, Nature Reviews Neuroscience.

[22]  Eugen Trinka,et al.  Effect of Transcranial Brain Stimulation for the Treatment of Alzheimer Disease: A Review , 2011, International journal of Alzheimer's disease.

[23]  Ann Marie Craig,et al.  Heterosynaptic Molecular Dynamics: Locally Induced Propagating Synaptic Accumulation of CaM Kinase II , 2009, Neuron.

[24]  Richard L. Huganir,et al.  Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking , 2006, Neuron.

[25]  P. Serrano,et al.  PKMζ Maintains Late Long-Term Potentiation by N-Ethylmaleimide-Sensitive Factor/GluR2-Dependent Trafficking of Postsynaptic AMPA Receptors , 2008, The Journal of Neuroscience.

[26]  J. Disterhoft,et al.  Learning Increases Intrinsic Excitability of Hippocampal Interneurons , 2013, The Journal of Neuroscience.

[27]  John F. Crary,et al.  Regulation of Protein Kinase Mζ Synthesis by Multiple Kinases in Long-Term Potentiation , 2007, The Journal of Neuroscience.

[28]  S. Sara.  The locus coeruleus and noradrenergic modulation of cognition , 2009, Nature Reviews Neuroscience.

[29]  E. Kandel.  The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses , 2001, Science.

[30]  Y. Goda,et al.  Homeostatic synaptic plasticity: from single synapses to neural circuits , 2012, Current Opinion in Neurobiology.

[31]  I. Izquierdo,et al.  Memory reconsolidation and its maintenance depend on L-voltage-dependent calcium channels and CaMKII functions regulating protein turnover in the hippocampus , 2013, Proceedings of the National Academy of Sciences.

[32]  R. Morris,et al.  Making memories last: the synaptic tagging and capture hypothesis , 2010, Nature Reviews Neuroscience.

[33]  Anna M. Lee,et al.  Prkcz null mice show normal learning and memory , 2012, Nature.

[34]  R. Muller,et al.  Inhibition of Protein Kinase Mζ Disrupts the Stable Spatial Discharge of Hippocampal Place Cells in a Familiar Environment , 2012, The Journal of Neuroscience.

[35]  Serge Laroche,et al.  Reconsolidation of memory: A decade of debate , 2012, Progress in Neurobiology.

[36]  Steven A. Connor,et al.  Fragile X mental retardation protein regulates heterosynaptic plasticity in the hippocampus. , 2011, Learning & memory.

[37]  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.

[38]  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.

[39]  Richard L. Huganir,et al.  Elongation Factor 2 and Fragile X Mental Retardation Protein Control the Dynamic Translation of Arc/Arg3.1 Essential for mGluR-LTD , 2008, Neuron.

[40]  Sreedharan Sajikumar,et al.  Making synapses strong: metaplasticity prolongs associativity of long-term memory by switching synaptic tag mechanisms. , 2014, Cerebral cortex.

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

[42]  P. Nguyen,et al.  "Silent" metaplasticity of the late phase of long-term potentiation requires protein phosphatases. , 2002, Learning & memory.

[43]  E. Kandel,et al.  Control of Memory Formation Through Regulated Expression of a CaMKII Transgene , 1996, Science.

[44]  Steven A. Connor,et al.  'Silent' priming of translation-dependent LTP by ß-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors. , 2010, Learning & memory.

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

[46]  Josué Haubrich,et al.  Memory reconsolidation allows the consolidation of a concomitant weak learning through a synaptic tagging and capture mechanism , 2013, Hippocampus.

[47]  Steven A. Connor,et al.  Activation of β‐adrenergic receptors facilitates heterosynaptic translation‐dependent long‐term potentiation , 2011, The Journal of physiology.

[48]  W. Abraham,et al.  Priming of short-term potentiation and synaptic tagging/capture mechanisms by ryanodine receptor activation in rat hippocampal CA1. , 2009, Learning & memory.

[49]  Paul De Koninck,et al.  CaMKII control of spine size and synaptic strength: Role of phosphorylation states and nonenzymatic action , 2010, Proceedings of the National Academy of Sciences.

[50]  John Lisman,et al.  The CaMKII/NMDAR complex as a molecular memory , 2013, Molecular Brain.

[51]  Ted Abel,et al.  Compartmentalized PKA signaling events are required for synaptic tagging and capture during hippocampal late-phase long-term potentiation. , 2006, European journal of cell biology.

[52]  Alcino J. Silva,et al.  Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. , 1998, Science.

[53]  Wickliffe C. Abraham,et al.  Emerging roles of metaplasticity in behaviour and disease , 2013, Trends in Neurosciences.

[54]  S. Sajikumar,et al.  Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD , 2004, Neurobiology of Learning and Memory.

[55]  P. Nguyen,et al.  Protein Synthesis Is Required for Synaptic Immunity to Depotentiation , 2003, The Journal of Neuroscience.

[56]  Paul De Koninck,et al.  Autonomous CaMKII Can Promote either Long-Term Potentiation or Long-Term Depression, Depending on the State of T305/T306 Phosphorylation , 2010, The Journal of Neuroscience.

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

[58]  Y. Dudai,et al.  Rapid Erasure of Long-Term Memory Associations in the Cortex by an Inhibitor of PKMζ , 2007, Science.

[59]  Roger L Redondo,et al.  Synaptic Tagging and Capture: Differential Role of Distinct Calcium/Calmodulin Kinases in Protein Synthesis-Dependent Long-Term Potentiation , 2010, The Journal of Neuroscience.

[60]  Yadin Dudai,et al.  Boundary conditions for the maintenance of memory by PKMzeta in neocortex. , 2009, Learning & memory.

[61]  Mark F. Bear,et al.  Heterosynaptic metaplasticity in the hippocampus in vivo: A BCM-like modifiable threshold for LTP , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[62]  T. Bliss,et al.  Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path , 1973, The Journal of physiology.

[63]  Heng-Ye Man,et al.  Homeostatic Regulation of AMPA Receptor Trafficking and Degradation by Light-Controlled Single-Synaptic Activation , 2011, Neuron.

[64]  S. Sajikumar,et al.  Metaplasticity governs compartmentalization of synaptic tagging and capture through brain-derived neurotrophic factor (BDNF) and protein kinase Mζ (PKMζ) , 2011, Proceedings of the National Academy of Sciences.

[65]  Eric R. Kandel,et al.  Expression of Constitutively Active CREB Protein Facilitates the Late Phase of Long-Term Potentiation by Enhancing Synaptic Capture , 2002, Cell.

[66]  Joseph E. LeDoux,et al.  reconsolidation of fear memories in the amygdala De novo mRNA synthesis is required for both consolidation and , 2008 .

[67]  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.

[68]  Hyun Jae Pi,et al.  Coupled Phosphatase and Kinase Switches Produce the Tristability Required for Long-Term Potentiation and Long-Term Depression , 2008, The Journal of Neuroscience.

[69]  R. Huganir,et al.  PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory , 2013, Nature.

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

[71]  Takashi Kawashima,et al.  Inverse Synaptic Tagging of Inactive Synapses via Dynamic Interaction of Arc/Arg3.1 with CaMKIIβ , 2012, Cell.

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

[73]  Edi Barkai,et al.  A cellular correlate of learning-induced metaplasticity in the hippocampus. , 2006, Cerebral cortex.

[74]  Todd Charlton Sacktor,et al.  Persistent Phosphorylation by Protein Kinase Mζ Maintains Late-Phase Long-Term Potentiation , 2005, The Journal of Neuroscience.

[75]  S. Sajikumar,et al.  Identification of Compartment- and Process-Specific Molecules Required for “Synaptic Tagging” during Long-Term Potentiation and Long-Term Depression in Hippocampal CA1 , 2007, The Journal of Neuroscience.

[76]  T. Sacktor,et al.  Protein kinase Mzeta is essential for the induction and maintenance of dopamine-induced long-term potentiation in apical CA1 dendrites. , 2010, Learning & memory.