Adenosine A2A-dopamine D2 receptor heteromers operate striatal function: impact on Parkinson's disease pharmacotherapeutics

Abstract

The basal ganglia (BG) assemble a series of deep gray matter structures forming recurrent loops that include the cortex and thalamus, and that participate in the regulation of a plethora of brain functions, including elicitation and learn ing of reward-and aversive stimuli-associated behaviors, motor activity control and sensorimotor gating (Brom berg-Martin et al., 2010). The striatum is the main input BG structure, thus it receives cortical glutamatergic projections from widespread areas of cortex and projects into other BG nuclei, including globus pallidus pars externa and the BG outputsglobus pallidus pars interna and substantia nigra pars reticulata. On the other hand, the substantia nigra pars compacta-ventral tegmental area (SNpc-VTA) modulates cortical-BG-thalamic circuits by means of dopaminergic innervation of the striatum. Interestingly, the main popula tion of striatal neurons, the medium spiny neurons (MSNs), provide the origin of two different striatal efferent pathways, the direct and indirect pathways (Schiffmann et al., 2007).