Distinct Long-Range Inhibitory and Excitatory Projections From the Mouse Superior Colliculus

The superior colliculus (SC) is extensively connected with cortical and subcortical nuclei to facilitate a range of cognitive and sensorimotor functions. Efferent projections from the SC vary by originating layer and topographic location. The present study identifies an additional determinant of efferent connectivity: released neurotransmitter. We show that long-range GABAergic and glutamatergic projection neurons produce distinct connectivity patterns in the mouse diencephalon, midbrain, and hindbrain. Targets strongly innervated by inhibitory vGAT+ neurons included the lateral dorsal, reuniens, anterior pretectal, and red nuclei, as well as the inferior colliculus. Targets of weaker vGAT+ innervation included the lateral habenula, ventral anterior-lateral complex, and reticular nucleus. In contrast, strongly innervated targets of excitatory vGlut2+ projections included the ventral medial, parafascicular, and tegmental reticular nuclei, whereas weaker innervation was present in the central medial intralaminar nucleus as well as in several contralateral thalamic and hindbrain nuclei. In shared efferent targets, vGAT+ and vGlut2+ projections often innervated different subregions or differed in cross-hemispheric connections, notably in the zona incerta, periaqueductal gray, and lateral posterior, pedunculopontine, pontine reticular, and tegmental reticular nuclei. These results collectively demonstrate an additional dimension of complexity in SC efferent connectivity in mice. Inhibitory projections may facilitate SC-mediated functions through a number of mechanisms independently of, or in concert with, excitatory projections. Future work examining the functional roles of SC long-range inhibition stands to elucidate these mechanisms and their contributions to behavior.