Brain-wide projections of mouse dopaminergic zona incerta neurons

The zona incerta (ZI) supports diverse behaviors including binge feeding, sleep/wake cycles, nociception, and hunting. This diversity of functions can be attributed to the heterogenous neurochemicals, cytoarchitecture, and efferent connections that characterize the ZI. The ZI is predominantly GABAergic, but we recently identified a subset of medial ZI GABA cells that co-express dopamine (DA), as marked by the enzyme tyrosine hydroxylase (TH). While the role of GABA within the ZI is well studied, little is understood about the function of ZI DA cells. To identify potential roles of ZI DA cells we mapped the efferent fiber projections from Th-cre ZI cells. We first validated a Th-cre;L10-Egfp mouse line and found that medial Egfp ZI cells were more likely to co-express TH-immunoreactivity (TH-ir). We thus delivered a cre-dependent virus into the medial ZI of Th-cre or Th-cre;L10-Egfp mice and selected two injection cases for full brain mapping. We selected the cases with the lowest (17%) and highest (53%) percentage of colocalization between TH-ir and virus transfected cells labelled with DsRed. Overall, DsRed-labelled fibers were observed throughout the brain and were most prominent within motor-related regions of the midbrain (MBmot), notably the periaqueductal grey area and superior colliculus. We also observed considerable DsRed-labelled fibers within the polymodal cortex associated regions of the thalamus (DORpm), including the paraventricular thalamic nucleus and nucleus of reunions. Overall, ZI DA cells displayed a similar connectivity profile to ZI GABA cells, suggesting that ZI DA cells may perform synergistic or opposing functions at the same target sites. List of RRIDsAB_2201528, AB_10013483, AB_11177031, AB_2340593, AB_2315778, SCR_016477 Three key points- Tyrosine hydroxylase immunoreactivity was more prominent in the medial zona incerta - Intersection points from two Th-cre injection cases revealed common target regions - Dopaminergic zona incerta cells project predominantly to motor-related brain regions