Dopaminergic control of synaptic plasticity in the dorsal striatum

Cortical glutamatergic and nigral dopaminergic afferents impinge on project ion spiny neurons of the striatum, providing the most significant inputs to this structure. Isolated activation of glutamate or dopamine (DA) receptor s produces short-term effects on striatal neurons, whereas the combined sti mulation of both glutamate and DA receptors is able to induce long-lasting modifications of synaptic excitability. Repetitive stimulation of corticost riatal fibres causes a massive release of both glutamate and DA in the stri atum and, depending on the glutamate receptor subtype preferentially activa ted, produces either long-term depression (LTD) or long-term potentiation ( LTP) of excitatory synaptic transmission. D1-like and D2-like DA receptors interact synergistically to allow LTD formation, while they operate in oppo sition during the induction phase of LTP. Corticostriatal synaptic plastici ty is severely impaired after chronic DA denervation and requires the stimu lation of DARPP-32, a small protein expressed in dopaminoceptive spiny neur ons which acts as a potent inhibitor of protein phosphatase-1. In addition, the formation of LTD and LTP requires the activation of PKG and PKA, respe ctively, in striatal projection neurons. These kinases appear to be stimula ted by the activation of D1-like receptors in distinct neuronal populations .