A Computational study of pre-synaptic re-uptake of dopamine on phosphorylation of DARPP-32

Abstract

The activity of mid brain dopamine (DA) neurons resembles the reward prediction error signal of the Temporal Difference (TD) model. Dopamine acting at Dl receptor activates adenylate cyclase through the coupling of Dl receptors with G s / o l f • The complex of adenylate cyclase activates and increases the intracellular levels of cAMP and thereby stim ulating cAMP dependent protein kinase and increasing the state of phosphorylation of DARPP-32 (dopamine and cyclic AMPregulated phosphoprotein, M, = 32,000). DARPP-32 plays an important role in autophosphorylation of calcium calmodulin dependent protein kinaseII (CaMKII) which is crucial for prolongation of long term potentiation (LTP). Here we verified the effect of pre-synaptic re-uptake of dopamine by dopamine transporter on the phosphorylation of DARPP-32 and found that the phosphorylation of DARPP-32 is unaffected by presynaptic re-uptake. Further we have seen that the DARPP-32 phosphorylation does not change with the change in the DA or DIR concentrations.

Role of CAMKII in reinforcement learning: a computational model of glutamate and dopamine signaling pathways

“…Our study produces the results that match well with the experimental and simulated data such as phosphorylation of DARPP-32 (Wanjerkhede and Bapi 2009), time course of phosphorylation of CaMKII, PKA activity, and percentage of open state of NMDAR (Wanjerkhede 2006). Ahn et al (2007) have investigated the mechanism of Ca 2+ -dependent regulation of Thr-75 by PP2A, and showed that PR72 (or B or PPP2R3A) regulatory subunit of PP2A is highly expressed in striatum.…”