Basal ganglia circuits play key roles in the control of motor behavior including action selection, and perturbations lead to movement disorders such as Parkinson’s disease or chorea (Gerfen and Surmeier, 2011, Grillner et al., 2005 and Kreitzer and Malenka, 2008). Basal ganglia output only accesses circuits in the

spinal cord indirectly through nuclei in the brainstem, which in turn establish connections to spinal interneurons and motor neurons (Grillner et al., 2005). To define the role of basal ganglia circuits in motor behavior, the activity of individual neurons can be monitored in behaving animals to determine patterns and changes as the animal learns to perform a task (Jog et al., 1999). Using such methods, a subset of nigrostriatal circuits was recently shown to play a highly specific BMS-754807 research buy role in initiation and termination of learned action sequences, a property blocked by selective elimination of striatal NMDAR1 (Jin and Costa, 2010). The function of basal ganglia circuits highlights the importance of precise synaptic input-output regulation and recent work begins to unravel the mechanisms

regulating synaptic specificity. The striatum is the basal ganglia input layer and combines many different presynaptic sources, including glutamatergic cortical and thalamic afferents and substantia nigra (SN)-derived dopaminergic input (Gerfen and Surmeier, 2011, Grillner et al., 2005 and Kreitzer and Malenka, 2008) (Figure 7B). GABAergic medium spiny neurons (MSNs) make up ca. 95% of all striatal neurons and can be divided into two main subpopulations based on expression of molecular markers (most notably check details distinct dopamine receptors [Drds]), connectivity, and function. Direct-pathway MSNs express Drd1a (D1) and project directly to basal ganglia output layers (GPi, internal segment of globus pallidus; SNr, substantia nigra pars reticularis), whereas indirect-pathway MSNs express Drd2 (D2) and have access to output layers only through intermediate relays (GPe, external

segment of globus pallidus; subthalamic nucleus). These two distinct pathways have been implicated in functionally opposing motor behaviors, movement facilitation for the D1-direct pathway, and movement inhibition Calpain for the D2-indirect pathway (Figure 7B). Making use of the striking molecular distinction between MSN subpopulations, this model was recently directly tested and essentially confirmed by the combination of MSN neuron subtype-specific Cre expression and conditional light-mediated activation of channelrhodopsin-2 in striatal neurons (Kravitz et al., 2010). Pathway divergence in the striatum raises the question of how the selection of synaptically appropriate input to D1- and D2-MSN subpopulations is regulated during development. A recent study provides evidence that Sema3e-PlxnD1 signaling between thalamic afferents and MSNs plays an important role in this process (Ding et al., 2012).