Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke differential motor and valence behaviors

The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) will inhibit locomotion and the globus pallidus externa (GPe) will enhance it. In mice, we use in vivo optogenetics to show that the GPe exerts non-canonical effects on locomotion while the SNr has no gross motor impact through inhibition of the pedunculopontine nucleus (PPN). We show that these structures mediate opposing effects on reward and that activation of substantia nigra pars compacta (SNc) dopaminergic axons in the PPN is rewarding. We use ex vivo whole-cell recording with optogenetics in mice to comprehensively dissect SNr and GPe synaptic connections to regionally- and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence.