Brain‐wide mapping of efferent projections of glutamatergic (Onecut3+) neurons in the lateral mouse hypothalamus

Abstract

AbstractAimThis study mapped the spatiotemporal positions and connectivity of Onecut3+ neuronal populations in the developing and adult mouse brain.MethodsWe generated fluorescent reporter mice to chart Onecut3+ neurons for brain‐wide analysis. Moreover, we crossed Onecut3‐iCre and Mapt‐mGFP (Tau‐mGFP) mice to visualize axonal projections. A dual Cre/Flp‐dependent AAV construct in Onecut3‐iCre cross‐bred with Slc17a6‐FLPo mice was used in an intersectional strategy to map the connectivity of glutamatergic lateral hypothalamic neurons in the adult mouse.ResultsWe first found that Onecut3 marks a hitherto undescribed Slc17a6+/Vglut2+ neuronal cohort in the lateral hypothalamus, with the majority expressing thyrotropin‐releasing hormone. In the adult, Onecut3+/Vglut2+ neurons of the lateral hypothalamus had both intra‐ and extrahypothalamic efferents, particularly to the septal complex and habenula, where they targeted other cohorts of Onecut3+ neurons and additionally to the neocortex and hippocampus. This arrangement suggests that intrinsic reinforcement loops could exist for Onecut3+ neurons to coordinate their activity along the brain's midline axis.ConclusionWe present both a toolbox to manipulate novel subtypes of hypothalamic neurons and an anatomical arrangement by which extrahypothalamic targets can be simultaneously entrained.