Patch and matrix striatonigral neurons differentially regulate locomotion.

The striatonigral neurons are known to promote locomotion 1,2 . These neurons reside in both the patch (also known as striosome) and matrix compartments of the dorsal striatum 3-5 . However, the specific contribution of patch and matrix striatonigral neurons to locomotion remain largely unexplored. Using molecular identifier Kringle-Containing Protein Marking the Eye and the Nose ( Kremen1 ) and Calbidin ( Calb1 ) 6 , we showed in mouse models that patch and matrix striatonigral neurons exert opposite influence on locomotion. While a reduction in neuronal activity in matrix striatonigral neurons precedes the cessation of locomotion, fiber photometry recording during self-paced movement revealed an unexpected increase of patch striatonigral neuron activity, indicating an inhibitory function. Indeed, optogenetic activation of patch striatonigral neurons suppressed locomotion, contrasting with the locomotion-promoting effect of matrix striatonigral neurons. Consistently, patch striatonigral neuron activation markedly inhibited dopamine release, whereas matrix striatonigral neuron activation initially promoted dopamine release. Moreover, the genetic deletion of inhibitory GABA-B receptor Gabbr1 in Aldehyde dehydrogenase 1A1-positive (ALDH1A1 + ) nigrostriatal dopaminergic neurons (DANs) completely abolished the locomotion-suppressing effect caused by activating patch striatonigral neurons. Together, our findings unravel a compartment-specific mechanism governing locomotion in the dorsal striatum, where patch striatonigral neurons suppress locomotion by inhibiting the activity of ALDH1A1 + nigrostriatal DANs.