Subcellular location of PKA controls striatal plasticity: stochastic simulations in spiny dendrites.

PLoS Computational Biology
Rodrigo F OliveiraKim T Blackwell

Abstract

Dopamine release in the striatum has been implicated in various forms of reward dependent learning. Dopamine leads to production of cAMP and activation of protein kinase A (PKA), which are involved in striatal synaptic plasticity and learning. PKA and its protein targets are not diffusely located throughout the neuron, but are confined to various subcellular compartments by anchoring molecules such as A-Kinase Anchoring Proteins (AKAPs). Experiments have shown that blocking the interaction of PKA with AKAPs disrupts its subcellular location and prevents LTP in the hippocampus and striatum; however, these experiments have not revealed whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. We have developed a large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines, based on published biochemical measurements, to investigate this question and to evaluate whether dopamine signaling exhibits spatial specificity post-synaptically. The model was stimulated with dopamine pulses mimicking those recorded in response to reward. Simulations show that PK...Continue Reading

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Citations

Sep 24, 2013·PloS One·Hans BlomHjalmar Brismar
Jun 8, 2013·Journal of Neuroscience Methods·K T Blackwell
Sep 11, 2013·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Kim T Blackwell, Joanna Jedrzejewska-Szmek
Jul 10, 2012·Neuropharmacology·Shao-Hui WangLing-Qiang Zhu
Nov 13, 2014·Frontiers in Cellular Neuroscience·Davide Calebiro, Isabella Maiellaro
Dec 30, 2014·Frontiers in Cellular Neuroscience·Kirill Gorshkov, Jin Zhang
Aug 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Roy S SongSusana R Neves
Mar 31, 2018·The European Journal of Neuroscience·Kim T BlackwellDavid M Lovinger
Feb 19, 2015·Nature Communications·Lu LiJean-Antoine Girault
Jul 12, 2013·Journal of Neurophysiology·R C EvansK T Blackwell
May 21, 2019·Cellular and Molecular Bioengineering·Matthew C PharrisTamara L Kinzer-Ursem
Mar 7, 2021·Cells·Giulietta Di BenedettoKonstantinos Lefkimmiatis

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