Fig. 4.

A schematic model for PINK1 function at the nigrostriatal and corticostriatal heterosynapse. This schematic model illustrates the neuromodulatory role of the nigrostriatal input at glutamatergic corticostriatal synapses of striatal medium spiny neurons (MSN). Coincident activation of convergent nigrostriatal dopaminergic and corticostriatal glutamergic inputs elicits synaptic release of DA and glutamate and activation of postsynaptic D1/D2 and NMDA/AMPA receptors, respectively. Activation of D1 receptors is necessary for the induction of LTP at corticostriatal synapses, whereas activation of both D1 and D2 receptors is necessary for induction of LTD. In the absence of PINK1, impaired release of DA from nigrostriatal terminals leads to reduced activation of postsynaptic D1 and D2 receptors, and consequent defects in both LTP and LTD.