dorsal/arxiv
View SchemaA Model of the Roles of Essential Kinases in the Induction and Expression of Late Long-Term Potentiation
| Authors | Paul Smolen, Douglas A. Baxter, John H. Byrne |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0601004 |
| URL | https://arxiv.org/abs/q-bio/0601004 |
| DOI | 10.1529/biophysj.105.072470 |
Abstract
The induction of late long-term potentiation (L-LTP) involves complex interactions among second messenger cascades. To gain insights into these interactions, a mathematical model was developed for L-LTP induction in the CA1 region of the hippocampus. The differential equation-based model represents actions of protein kinase A (PKA), MAP kinase (MAPK), and CaM kinase II (CAMKII) in the vicinity of the synapse, and activation of transcription by CaM kinase IV (CAMKIV) and MAPK. L-LTP is represented by increases in a synaptic weight. Simulations suggest that steep, supralinear stimulus-response relationships between stimuli (elevations in [Ca2+]) and kinase activation are essential for translating brief stimuli into long-lasting gene activation and synaptic weight increases. Convergence of multiple kinase activities to induce L-LTP helps to generate a threshold whereby the amount of L-LTP varies steeply with the number of tetanic electrical stimuli. The model simulates tetanic, theta-burst, pairing-induced, and chemical L-LTP, as well as L-LTP due to synaptic tagging. The model also simulates inhibition of L-LTP by inhibition of MAPK, CAMKII, PKA, or CAMKIV. The model predicts results of experiments to delineate mechanisms underlying L-LTP induction and expression. For example, the cAMP antagonist RpcAMPs, which inhibits L-LTP induction, is predicted to inhibit ERK activation. The model also appears useful to clarify similarities and differences between hippocampal L-LTP and long-term synaptic strengthening in other systems.
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"abstract": "The induction of late long-term potentiation (L-LTP) involves complex\ninteractions among second messenger cascades. To gain insights into these\ninteractions, a mathematical model was developed for L-LTP induction in the CA1\nregion of the hippocampus. The differential equation-based model represents\nactions of protein kinase A (PKA), MAP kinase (MAPK), and CaM kinase II\n(CAMKII) in the vicinity of the synapse, and activation of transcription by CaM\nkinase IV (CAMKIV) and MAPK. L-LTP is represented by increases in a synaptic\nweight. Simulations suggest that steep, supralinear stimulus-response\nrelationships between stimuli (elevations in [Ca2+]) and kinase activation are\nessential for translating brief stimuli into long-lasting gene activation and\nsynaptic weight increases. Convergence of multiple kinase activities to induce\nL-LTP helps to generate a threshold whereby the amount of L-LTP varies steeply\nwith the number of tetanic electrical stimuli. The model simulates tetanic,\ntheta-burst, pairing-induced, and chemical L-LTP, as well as L-LTP due to\nsynaptic tagging. The model also simulates inhibition of L-LTP by inhibition of\nMAPK, CAMKII, PKA, or CAMKIV. The model predicts results of experiments to\ndelineate mechanisms underlying L-LTP induction and expression. For example,\nthe cAMP antagonist RpcAMPs, which inhibits L-LTP induction, is predicted to\ninhibit ERK activation. The model also appears useful to clarify similarities\nand differences between hippocampal L-LTP and long-term synaptic strengthening\nin other systems.",
"arxiv_id": "q-bio/0601004",
"authors": [
"Paul Smolen",
"Douglas A. Baxter",
"John H. Byrne"
],
"categories": [
"q-bio.NC",
"q-bio.MN"
],
"doi": "10.1529/biophysj.105.072470",
"title": "A Model of the Roles of Essential Kinases in the Induction and Expression of Late Long-Term Potentiation",
"url": "https://arxiv.org/abs/q-bio/0601004"
},
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