Biochemical Signaling Networks Decode Temporal Patterns of Synaptic Input

Synapses exhibit a wide repertoire of responses to different temporal patterns of synaptic input. Many of these responses are expressed as short and long-term changes in synaptic strength. Electrical properties of channels and calcium buildup can account for rapid aspects of pattern decoding, but it is not clear how more complex input patterns, especially those lasting over many minutes, could be discriminated. This paper shows that a network of signaling pathways can discriminate between complex input patterns lasting tens of minutes, and can give rise to distinct combinatorial patterns of biochemical signaling activity in pathways involved in synaptic change. Regulatory signaling input can alter and even reverse the strengths of responses to input patterns. Thus the synaptic signaling network may function as a temporal decoder that transforms patterns from the time domain into the domain of chemical signaling. This may underlie different synaptic responses to different stimulus patterns.

[1]  Eric R Kandel,et al.  ERK Plays a Regulatory Role in Induction of LTP by Theta Frequency Stimulation and Its Modulation by β-Adrenergic Receptors , 1999, Neuron.

[2]  James M. Bower,et al.  Sensitivity of Synaptic Plasticity to the Ca2+ Permeability of NMDA Channels: A Model of Long-Term Potentiation in Hippocampal Neurons , 1993, Neural Computation.

[3]  R. Colbran,et al.  Differential Inactivation of Postsynaptic Density‐Associated and Soluble Ca2+/Calmodulin‐Dependent Protein Kinase II by Protein Phosphatases 1 and 2A , 1997, Journal of neurochemistry.

[4]  I. V. Orekhova,et al.  The neuromuscular transform: the dynamic, nonlinear link between motor neuron firing patterns and muscle contraction in rhythmic behaviors. , 2000, Journal of neurophysiology.

[5]  A Aszódi,et al.  Signal convergence on protein kinase A as a molecular correlate of learning. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[6]  T. Teyler,et al.  Two forms of long-term potentiation in area CA1 activate different signal transduction cascades. , 1996, Journal of neurophysiology.

[7]  A J Hudspeth,et al.  A model for electrical resonance and frequency tuning in saccular hair cells of the bull‐frog, Rana catesbeiana. , 1988, The Journal of physiology.

[8]  R. Birge,et al.  v-Crk Modulation of Growth Factor-induced PC12 Cell Differentiation Involves the Src Homology 2 Domain of v-Crk and Sustained Activation of the Ras/Mitogen-activated Protein Kinase Pathway (*) , 1995, The Journal of Biological Chemistry.

[9]  J E Ferrell,et al.  The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. , 1998, Science.

[10]  D V Buonomano,et al.  Decoding Temporal Information: A Model Based on Short-Term Synaptic Plasticity , 2000, The Journal of Neuroscience.

[11]  Ravi Iyengar,et al.  Robustness of the bistable behavior of a biological signaling feedback loop. , 2001, Chaos.

[12]  L. Abbott,et al.  Synaptic plasticity: taming the beast , 2000, Nature Neuroscience.

[13]  J. Lisman The CaM kinase II hypothesis for the storage of synaptic memory , 1994, Trends in Neurosciences.

[14]  W. Levy,et al.  Insights into associative long-term potentiation from computational models of NMDA receptor-mediated calcium influx and intracellular calcium concentration changes. , 1990, Journal of neurophysiology.

[15]  J. Bos,et al.  cAMP antagonizes p21ras‐directed activation of extracellular signal‐regulated kinase 2 and phosphorylation of mSos nucleotide exchange factor. , 1993, The EMBO journal.

[16]  J. Pouysségur,et al.  The Dual Specificity Mitogen-activated Protein Kinase Phosphatase-1 and −2 Are Induced by the p42/p44MAPK Cascade* , 1997, The Journal of Biological Chemistry.

[17]  E. Marder,et al.  Activity-dependent changes in the intrinsic properties of cultured neurons. , 1994, Science.

[18]  Lawrence M. Grover,et al.  Two components of long-term potentiation induced by different patterns of afferent activation , 1990, Nature.

[19]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[20]  Upinder S Bhalla,et al.  Mechanisms for temporal tuning and filtering by postsynaptic signaling pathways. , 2002, Biophysical journal.

[21]  R. Traub,et al.  A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances. , 1991, Journal of neurophysiology.

[22]  J. Young,et al.  Differential maintenance and frequency-dependent tuning of LTP at hippocampal synapses of specific strains of inbred mice. , 2000, Journal of neurophysiology.

[23]  M. Kennedy,et al.  Distinct forebrain and cerebellar isozymes of type II Ca2+/calmodulin-dependent protein kinase associate differently with the postsynaptic density fraction. , 1985, The Journal of biological chemistry.

[24]  H. Markram,et al.  Redistribution of synaptic efficacy between neocortical pyramidal neurons , 1996, Nature.

[25]  D. Linden,et al.  Long-term synaptic depression in the mammalian brain , 1994, Neuron.

[26]  R. Douglas Fields,et al.  Action Potential-Dependent Regulation of Gene Expression: Temporal Specificity in Ca2+, cAMP-Responsive Element Binding Proteins, and Mitogen-Activated Protein Kinase Signaling , 1997, The Journal of Neuroscience.

[27]  T. H. Brown,et al.  Dendritic spines: convergence of theory and experiment. , 1992, Science.

[28]  W A Wilson,et al.  Induction and reversal of long-term potentiation by low- and high- intensity theta pattern stimulation , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  S. Hooper Transduction of temporal patterns by single neurons , 1998, Nature Neuroscience.

[30]  Karl Deisseroth,et al.  Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology , 2001, Nature Neuroscience.

[31]  D. Debanne,et al.  The role of dendritic filtering in associative long-term synaptic plasticity. , 1999, Learning & memory.

[32]  P. Kostyuk,et al.  Calcium Signalling in the Nervous System , 1995 .

[33]  D. Johnston,et al.  Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs , 1997 .

[34]  T. Bliss,et al.  Brain-Derived Neurotrophic Factor Induces Long-Term Potentiation in Intact Adult Hippocampus: Requirement for ERK Activation Coupled to CREB and Upregulation of Arc Synthesis , 2002, The Journal of Neuroscience.

[35]  M. W. Brown,et al.  An experimental test of the role of postsynaptic calcium levels in determining synaptic strength using perirhinal cortex of rat , 2001, The Journal of physiology.

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

[37]  Martin D. Bootman,et al.  The elemental principles of calcium signaling , 1995, Cell.

[38]  J. White,et al.  Networks of interneurons with fast and slow gamma-aminobutyric acid type A (GABAA) kinetics provide substrate for mixed gamma-theta rhythm. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[39]  S. Shenolikar,et al.  Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. , 1998, Science.

[40]  P. Stanton,et al.  LTD, LTP, and the sliding threshold for long‐term synaptic plasticity , 1996, Hippocampus.

[41]  J. Bower,et al.  The Book of GENESIS , 1998, Springer New York.

[42]  U. Bhalla,et al.  Emergent properties of networks of biological signaling pathways. , 1999, Science.

[43]  U. Bhalla,et al.  Complexity in biological signaling systems. , 1999, Science.

[44]  E. Marder,et al.  Activity-dependent regulation of conductances in model neurons. , 1993, Science.

[45]  M. H. Cobb,et al.  Dual MAP kinase pathways mediate opposing forms of long-term plasticity at CA3–CA1 synapses , 2000, Nature Neuroscience.

[46]  Lubert Stryer,et al.  Dual role of calmodulin in autophosphorylation of multifunctional cam kinase may underlie decoding of calcium signals , 1994, Neuron.