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A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity (Nakano et al. 2010)
A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32), as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA), protein phosphatase 2A (PP2A), and the phosphorylation site at threonine 75 of DARPP-32 (Thr75) served as the major switch for inducing LTD and LTP. The present model elucidated the mechanisms involved in bidirectional regulation of corticostriatal synapses and will allow for further exploration into causes and therapies for dysfunctions such as drug addiction."
  • Neostriatum medium spiny direct pathway GABA cell Show Other
  • Nakano T, Doi T, Yoshimoto J, Doya K (2010) Show Other
  • Nakano, Takashi [nakano.takashi at gmail.com] Show Other
nakano.takashi@gmail.com
Nakano, Takashi
PMID: 20169176
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Revisions: 6
Last Time: 9/5/2012 1:37:30 PM
Reviewer: Tom Morse - MoldelDB admin
Owner: Tom Morse - MoldelDB admin