Third pathway in the cortico-basal ganglia loop: Neurokinin B-producing striatal neurons modulate cortical activity...

In the cortico-basal ganglia loop, striatal regions serve as 'entrances' to the basal ganglia, receiving massive inputs from the cerebral cortex and sending 'direct' and 'indirect' pathways to the output nuclei of the basal ganglia. However, we have recently identified a new striatofugal subgroup which produces neurokinin B (NKB). Although NKB-producing neurons constitute a minority of striatal neurons, this subgroup is distinguished by the unique distribution and chemical characteristics. NKB-producing striatal neurons are distributed in association with mu-opioid receptor localization, and rarely express DARPP32, which is produced by the major striatofugal neurons and coupled with dopaminergic signaling. Further interestingly NKB-producing striatal neurons send axons to basal forebrain regions, but not to the main target regions of striatal outflow, pallidal or mesencephalic regions. In the basal forebrain, some GABAergic inhibitory neurons express NK3 receptor, selective receptor for NKB, and directly send axons to the cerebral cortex. The NK3-expressing neurons show different electrical properties from cholinergic basal forebrain neurons, and display facilitatory responses to stimulation of NK3 receptor. These findings strongly suggest that NKB-producing striatal neurons and NK3-expressing basal forebrain neurons constitute a third pathway which bypasses the common output nuclei of the basal ganglia, and more directly control or modulate cortical activity.