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Role of DARPP-32 and ARPP-21 in the Emergence of Temporal Constraints on Striatal Calcium and Dopamine Integration
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
2016 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 12, no 9, e1005080Article in journal (Refereed) Published
Abstract [en]

In reward learning, the integration of NMDA-dependent calcium and dopamine by striatal projection neurons leads to potentiation of corticostriatal synapses through CaMKII/PP1 signaling. In order to elicit the CaMKII/PP1-dependent response, the calcium and dopamine inputs should arrive in temporal proximity and must follow a specific (dopamine after calcium) order. However, little is known about the cellular mechanism which enforces these temporal constraints on the signal integration. In this computational study, we propose that these temporal requirements emerge as a result of the coordinated signaling via two striatal phosphoproteins, DARPP-32 and ARPP-21. Specifically, DARPP-32-mediated signaling could implement an input-interval dependent gating function, via transient PP1 inhibition, thus enforcing the requirement for temporal proximity. Furthermore, ARPP-21 signaling could impose the additional input-order requirement of calcium and dopamine, due to its Ca2+/calmodulin sequestering property when dopamine arrives first. This highlights the possible role of phosphoproteins in the temporal aspects of striatal signal transduction.

Place, publisher, year, edition, pages
PLoS , 2016. Vol. 12, no 9, e1005080
National Category
Bioinformatics and Systems Biology Neurosciences
URN: urn:nbn:se:kth:diva-193601DOI: 10.1371/journal.pcbi.100508OAI: diva2:1032989
EU, Horizon 2020EU, FP7, Seventh Framework ProgrammeSwedish eā€Science Research CenterSwedish Research Council

QC 20161010

Available from: 2016-10-05 Created: 2016-10-05 Last updated: 2016-10-10Bibliographically approved

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Nair, Anu G.Kotaleski, Jeanette Hellgren
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