While the interconnection of monoaminergic nuclei, namely the Raphe nucleus, Locus coeruleus (LC) and Ventral Tegmental Area (VTA) is widely acknowledged for its pivotal role in mediating diverse cerebral functions, the true complexity lies in the nuanced neuroanatomical and neurochemical diversity within each system. Recent discoveries have brought to light distinctive neuronal populations within the raphe nucleus or the LC, both projecting specifically to the VTA, main nucleus for dopamine secretion. The raphe nucleus is a neurochemically diverse hub, hosting not only serotonergic neurons but also GABAergic, DAergic and glutamatergic cells. The LC has been acknowledged for its widespread noradrenergic projections throughout the brain, its functional impact on the VTA is starting to be known, however its projections onto the raphe nucleus are poorly documented. Our objective is to investigate the interconnections among the monoaminergic systems, considering the multifaceted cellular heterogeneity that defines their functionality. Especially, in this study, we focused on the regulation of the raphe and VTA nuclei by LC neurons. Employing tissue clearing and immunohistochemistry methods, we aim to meticulously map both pre- and post-synaptic components of LC-NE neurons projecting to the VTA and Raphe nucleus. Using viral strategies and immunohistochemistry on mice, we analyzed the synaptic connections at cell-type specific level of the LC-Raphe-VTA pathways. This work will allow to build a comprehensive study of functional complexity within monoaminergic systems. Such an exploration aims to shed light on their roles in mediating various psychiatric disorders.