Algebraic Method for the Analysis of Signaling Crosstalk

A unified mathematical description that expresses the characteristics of whole systems is necessary for an understanding of signal transduction cascades. In this study we explore an algebraic method, named extreme signaling flow, enhanced from the concept of extreme pathway, to analyze signal transduction systems. This method enables us to represent the long-term potentiation (LTP) and the long-term depression (LTD) of hippocampal neuronal plasticity in an integrated simulation model. The model is validated by comparing the results of redundancy, reaction participation, and in silico knockout analysis with biological knowledge available from the literature. The following properties are assumed in these computational analyses: (1) LTP is fault-tolerant under network modification, (2) protein kinase C and MAPK have numerous routes to LTP induction, (3) calcium-calmodulin kinase II has a few routes to LTP induction, and (4) calcineurin has many routes to LTD induction. These results demonstrate that our approach produces an integrated framework for analyzing properties of large-scale systems with complicated signal transduction.

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Two forms of long-term potentiation in area CA1 activate different signal transduction cascades

Journal of Neurophysiology ◽

10.1152/jn.1996.76.5.3038 ◽

1996 ◽

Vol 76 (5) ◽

pp. 3038-3047 ◽

Cited By ~ 122

Author(s):

I. Cavus ◽

T. Teyler

Keyword(s):

Signal Transduction ◽

Nmda Receptor ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Protein Kinase Inhibitors ◽

Area Ca1 ◽

Term Potentiation

1. The effects of protein kinase inhibitors on N-methyl-D-aspartate (NMDA)-receptor-mediated, voltage-dependent calcium channel (VDCC)-mediated, and 100-Hz long-term potentiation (LTP) were studied in area CA1 of rat hippocampal slices. 2. A 25-Hz tetanus induced a quickly developing potentiation that was blocked by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV) and was not affected by the L-type VDCC inhibitor nifedipine, suggesting that it was mediated by NMDA receptors (NMDA-LTP). 3. Application of a 200-Hz tetanus in APV induced a slowly developing NMDA-receptor-independent potentiation that was blocked by nifedipine and thus named VDCC-LTP. NMDA- and VDCC-LTP reached comparable magnitudes despite their different induction parameters and developmental kinetics. 4. Bath perfusion of the broad-spectrum serine/threonine kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) blocked NMDA-LTP but not VDCC-LTP, whereas the tyrosine kinase inhibitors genistein and lavendustin A blocked VDCC-LTP but not NMDA-LTP. These results suggest a differential involvement of H-7-sensitive serine/threonine kinases and tyrosine kinases in the two forms of LTP. 5. Tetanization of 200 Hz in control media resulted in a compound potentiation twice as large as NMDA- or VDCC-LTP, implying that the two forms of LTP did not facilitate or reduce each other's expression. The often-used 100-Hz tetanus (1 s twice) induced a potentiation that was comparable in size with the 200-Hz compound LTP. Nifedipine, genistein, and lavendustin A reduced the 100-Hz LTP by approximately 50%, suggesting that this LTP is also a compound potentiation consisting of NMDA- and VDCC-mediated components and their corresponding signal transduction pathways.

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Large-scale study of phosphoproteins involved in long-term potentiation in the rat dentate gyrusin vivo

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2008.06280.x ◽

2008 ◽

Vol 27 (11) ◽

pp. 2985-2998 ◽

Cited By ~ 5

Author(s):

Solenne Chardonnet ◽

Pierre Le Marechal ◽

Hélène Cheval ◽

Jean-Pierre Le Caer ◽

Paulette Decottignies ◽

...

Keyword(s):

Large Scale ◽

Long Term Potentiation ◽

Large Scale Study ◽

Term Potentiation

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Differential roles of signal transduction mechanisms in long-term potentiation of excitatory synaptic transmission induced by activation of group I mGluRs in the spinal trigeminal subnucleus oralis

Brain Research Bulletin ◽

10.1016/j.brainresbull.2014.08.003 ◽

2014 ◽

Vol 108 ◽

pp. 37-43 ◽

Cited By ~ 5

Author(s):

Dong-ho Youn

Keyword(s):

Signal Transduction ◽

Synaptic Transmission ◽

Long Term Potentiation ◽

Excitatory Synaptic Transmission ◽

Group I ◽

Term Potentiation ◽

Transduction Mechanisms ◽

Group I Mglurs

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Why Calcium-Stimulated Adenylyl Cyclases?

Physiology ◽

10.1152/physiol.00010.2004 ◽

2004 ◽

Vol 19 (5) ◽

pp. 271-276 ◽

Cited By ~ 73

Author(s):

Gregory D. Ferguson ◽

Daniel R. Storm

Keyword(s):

Signal Transduction ◽

Neuronal Activity ◽

Critical Role ◽

Long Term Potentiation ◽

Long Term Memory ◽

Adenylyl Cyclases ◽

Term Memory ◽

Term Potentiation ◽

Dependent Signal

The Ca2+/calmodulin-stimulated adenylyl cyclases, AC1 and AC8, play a critical role in several forms of neuroplasticity, including long-lasting long-term potentiation (L-LTP) and long-term memory (LTM). By coupling neuronal activity and Ca2+ increases to the production of cAMP, AC1 and AC8 activate cAMP-dependent signal transduction and transcriptional pathways critical for L-LTP and LTM.

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