Fig. 1: Schematic summarising the major inputs and outputs connecting with the ventral tegmental area (VTA) dopamine neurons.

In the adult brain, dopaminergic neurons exist as a heterogenous group of cells localised predominately in the VTA and substantia nigra [190, 204, 205]. From these areas, dopaminergic projections arising from the VTA extend to limbic (mesolimbic) and cortical (mesocortical) regions, and from the substantia nigra to striatal (nigrostriatal), regions of the brain [206]. Given the overlap in common projections between the dopaminergic mesolimbic and mesocortical pathways, these two systems are often referred to the mesocorticolimbic pathway collectively [204] (Fig. 1). Mesolimbic and mesocortical pathways originating in the VTA send dopamine projections to the NAc and olfactory tubercle, and to limbic regions including the amygdala, hippocampus and frontal cortices through the medial forebrain bundle [207,208,209]. The VTA also sends and receives extensive reciprocal innervations from these same brain areas, as well as many others areas including the lateral hypothalamus, lateral habenula, dorsal raphe nucleus and periaqueductal grey [207,208,209]. In essence, dopamine neurons in the midbrain are densely connected with the rest of brain, where dopamine signalling is heavily influenced by descending projections, and in turn heavily influences processing in these regions to drive associative learning [34, 35, 39, 40, 44, 47, 118, 146, 210, 211]. Abbreviations: Amyg Amygdala, DRN Dorsal Raphe Nucleus, LDTg laterodorsal tegmentum nucleus, LH Lateral Hypothalamus, LHb Lateral Habenula, NAc Nucleus Accumbens, mPFC Medial Prefrontal Cortex, PAG Periaqueductal Grey, RMTg Rostromedial Mesopontine Tegmental Nucleus, VP Ventral Pallidum, VTA Ventral Tegmental Area.