This Week in The Journal

Most neurons in the external segment of the globus pallidus (GPe) contribute to the indirect pathway from the dorsal striatum to the output nuclei of the basal ganglia, relaying information from the striatum to the subthalamic nucleus. But 25% of GPe neurons project back to the striatum. These neurons, called arkypallidal neurons, were recently proposed to cancel movements that are in the preparation stage (Mallet, et al. 2016 Neuron, 89: 308). They are distinguishable from prototypic indirectpathway GPe neurons not only by their projections, but also by their firing and protein-expression patterns. Glajch et al. report that most pallidostriatal neurons express the transcription factor Npas1 (although some expressed parvalbumin, a marker of prototypic GPe neurons). Npas1-expressing GPe neurons densely innervated the striatum, and optical stimulation of their axon terminals evoked IPSCs in both directand indirect-pathway medium spiny projection neurons (SPNs), as well as in interneurons. Evoked IPSCs were larger in indirect-pathway SPNs than in direct-pathway SPNs, and this difference was at least partially attributable to the fact that GPe inputs were closer to the soma in indirect-pathway SPNs. Previous work has shown that loss of dopaminergic inputs to the striatum—as occurs in Parkinson’s disease—increases activity in indirect-pathway SPNs, thus increasing inhibition of SPN targets in the GPe. How does this affect pallidostriatal feedback? Glajch et al. found that loss of dopaminergic input increased the amplitude of IPSCs evoked by Npas1-expressing GPe neurons in both directand indirectpathway SPNs. In direct-pathway SPNs, this appeared to result from GPe inputs moving closer to the soma, whereas in indirectpathway SPNs it was attributable to increased GABA receptor expression. In both cases, however, the result was a decrease in the excitability of SPNs. This work shows that pallidostriatal neurons inhibit SPNs in both the direct pathway, which is thought to facilitate production of desired behaviors, and in the indirect pathway, which is thought to suppress conflicting behaviors. Thus, these projections may not only cancel planned movements, but also facilitate production of an alternative action. Optical activation of Npas1-expressing neurons in vivo should test this hypothesis to further elucidate the function of pallidostriatal projections.