Targeting Neuronal Populations of the Striatum

The striatum is critically involved in motor and motivational functions. The dorsal striatum, caudate–putamen, is primarily implicated in motor control and the learning of habits and skills, whereas the ventral striatum, the nucleus accumbens, is essential for motivation and drug reinforcement. The GABA medium-sized spiny neurons (MSNs, about 95% of striatal neurons), which are targets of the cerebral cortex and the midbrain dopaminergic neurons, form two pathways. The dopamine D(1) receptor-positive (D(1)R) striatonigral MSNs project to the medial globus pallidus and substantia nigra pars reticulata (direct pathway) and co-express D(1)R and substance P, whereas dopamine D(2) receptor-positive (D(2)R) striatopallidal MSNs project to the lateral globus pallidus (indirect pathway) and co-express D(2)R, adenosine A(2A) receptor (A(2A)R) and enkephalin (Enk). The specific role of the two efferent pathways in motor and motivational control remained poorly understood until recently. Indeed, D(1)R striatonigral and D(2)R striatopallidal neurons, are intermingled and morphologically indistinguishable, and, hence, cannot be functionally dissociated with techniques such as chemical lesions or surgery. In view of the still debated respective functions of projection D(2)R striatopallidal and D(1)R striatonigral neurons and striatal interneurons, both in motor control and learning but also in more cognitive processes such as motivation, the present review sum up the development of new models and techniques (bacterial artificial chromosome transgenesis, optogenetic, viral transgenesis) allowing the selective targeting of these striatal neuronal populations in adult animal brain to understand their specific roles.