Dopaminergic control of synaptic plasticity in the dorsal striatum

Abstract

Cortical glutamatergic and nigral dopaminergic afferents impinge on projection spiny neurons of the striatum, providing the most significant inputs to this structure. Isolated activation of glutamate or dopamine (DA) receptors produces short-term effects on striatal neurons, whereas the combined stimulation of both glutamate and DA receptors is able to induce long-lasting modifications of synaptic excitability. Repetitive stimulation of corticostriatal fibres causes a massive release of both glutamate and DA in the striatum and, depending on the glutamate receptor subtype preferentially activated, 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 opposition during the induction phase of LTP. Corticostriatal synaptic plasticity is severely impaired after chronic DA denervation and requires the stimulation of DARPP-32, a small protein expressed in dopaminoceptive spiny neurons 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, respectively, in striatal projection neurons. These kinases appear to be stimulated by the activation of D1-like receptors in distinct neuronal populations.

A Critical Interaction between Dopamine D2 Receptors and Endocannabinoids Mediates the Effects of Cocaine on Striatal GABAergic Transmission

“…The endocannabinoid-dependent inhibition of GABA inputs might favor synaptic plasticity at excitatory corticostriatal synapses by enhancing the level of postsynaptic depolarization required for the induction of both LTP and LTD (Centonze et al, 2001). In this line, it has recently been shown that cannabinoid-dependent inhibition of GABA transmission may actually facilitate the emergence of synaptic plasticity at excitatory synapses in the hippocampus (Carlson et al, 2002).…”

Motor-Skill Learning-Associated Gene Regulation in the Striatum: Effects of Cocaine

“…For example, long-term potentiation (LTP) and long-term depression (LTD) induced by high-frequency stimulation are forms of synaptic plasticity that have long been considered candidate processes for learning and memory. Acute high-frequency activation of cortical inputs is well known to produce LTP or LTD at the corticostriatal synapse (Calabresi et al, 1996;Centonze et al, 2001;Reynolds and Wickens, 2002;Gerdeman et al, 2003;Mahon et al, 2004), and such effects have been implicated in altered gene induction after psychostimulant treatments (Graybiel et al, 2000). Importantly, there is evidence that, in vivo, lowfrequency stimulation can be sufficient to induce LTP (Charpier et al, 1999).…”

“…Importantly, there is evidence that, in vivo, lowfrequency stimulation can be sufficient to induce LTP (Charpier et al, 1999). Both LTP and LTD are dependent on dopamine input (Calabresi et al, 1996;Centonze et al, 2001;Reynolds and Wickens, 2002), with low dopamine levels apparently favoring LTD and high dopamine levels producing LTP at the corticostriatal synapse (Reynolds and Wickens, 2002). Notably, such LTP is blocked by D1 receptor antagonism (Kerr and Wickens, 2001;Reynolds et al, 2001;Centonze et al, 2003).…”

Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum

“…If reinforcement involves long-term modifications in the strength of striatal input signals [9,102,124], then abnormalities in the relative strength of these inputs would prevent reinforcement of appropriate inputs. However, DA is also necessary for striatal plasticity [21,25]. DA's role in learning is, therefore, likely to include not only a selective gate-keeping function for glutamate inputs, but also a direct role in promoting plasticity of currently active synapses.…”