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

The activity of mid brain dopamine (DA) neurons resembles the reward prediction error signal of the temporal difference (TD) model. Dopamine acting at D1 receptor activates adenylate cyclase through the coupling of D1 receptors with G_s/olf. The complex of adenylate cyclase activates and increases the intracellular levels of cAMP and thereby stimulating cAMP dependent protein kinase and increasing the state of phosphorylation of DARPP-32 (dopamine and cyclic AMP-regulated 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 pre-synaptic re-uptake. Further we have seen that the DARPP-32 phosphorylation does not change with the change in the DA or D1R concentrations.