Regulation of corticostriatal synaptic plasticity by G protein-coupled receptors

Abstract

Dopamine modulation of excitatory neurotransmission is critical in the control of movement, emotion and reward. In the striatum, medium size spiny neurons (MSNs) are responsible for the integration of cortical and thalamic information that flows through parallel, partly overlapping, loops and determines adequate experience-dependent responses. Dopamine acts on MSNs through two sets of G protein-coupled receptors (GPCRs), the D1-like and D2-like receptors, which can have opposing or synergistic downstream effects. Notably, these two types of striatal dopamine receptors are segregated into the striatonigral (direct) and striatopallidal (indirect) projecting neurons. Thus, dopamine receptor expression determines the morphological and functional neuronal phenotype of MSNs. Moreover, dopamine regulates glutamatergic corticostriatal transmission, critically controlling the induction of long-term potentiation and long-term depression at these synapses, regulating striatal synaptic plasticity. In addition to dopamine receptors, the induction and expression of plasticity mechanisms is regulated by other GPCRs, most importantly adenosine A₂(A) receptors, metabotropic glutamate mGluR5 receptors and endocannabinoid CB1 receptors. This review focuses on synaptic modulation and plasticity on excitatory corticostriatal synapses by GPCRs.