title: Role of DARPP-32 and ARPP-21 in the Emergence of Temporal Constraints on Striatal Calcium and Dopamine Integration.
abstract: 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.
authors: Science for Life Laboratory, School of Computer Science and Communication, KTH Royal Institute of Technology, Stockholm, Sweden.|National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.|Manipal University, Manipal, India.
authors: Anu G
authors: 0000-0002-1952-9583
authors: AG
authors: Nair
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
authors: Upinder S
authors: US
authors: Bhalla
authors: Science for Life Laboratory, School of Computer Science and Communication, KTH Royal Institute of Technology, Stockholm, Sweden.|Department of Neuroscience, Karolinska Institutet, Solna, Sweden.
authors: Jeanette
authors: J
authors: Hellgren Kotaleski
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D019295:Computational Biology; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D010750:Phosphoproteins; C061368:cyclic AMP-regulated phosphoprotein ARPP-21; D002118:Calcium; D004298:Dopamine