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. 2014 Nov 17;5:253. doi: 10.3389/fphar.2014.00253

FIGURE 2.

FIGURE 2

Schematic illustration of inputs to and outputs from VTA dopaminergic neurons. VTA dopaminergic neurons project to the NAc (required for responding to reward prediction cues), medial prefrontal cortex (implicated in working memory and attentional processes), basolateral amygdala (implicated in emotion, reward, fear conditioning, and avoidance) and hippocampus (memory; green, dopaminergic components). Notably, VTA dopaminergic outputs are extensively differentiated with distinct projections from specific populations of dopaminergic neurons to specific downstream structures. In this way, mesolimbic dopaminergic activity functions in seemingly contradictory processes such as reward and aversion (McCullough et al., 1993; Stevenson et al., 2003; Baliki et al., 2010; McCutcheon et al., 2012). That is, the functions of ventral tegmental area dopaminergic projections is determined by network topology rather than simply by the choice of neurotransmitter. VTA dopaminergic neurons receive dense GABAergic modulatory input from numerous extrinsic structures and from GABAergic interneurons within the ventral tegmental area itself (blue). GABAergic projections to the VTA has been identified from the NAc (Nauta et al., 1978); ventral pallidum (Haber et al., 1985); RMTg (Jhou et al., 2009) and the pedunculopontine tegmental nucleus/lateral dorsal tegmentun (Omelchenko and Sesack, 2005; Good and Lupica, 2009). These neurons are also modulated by excitatory inputs (red) from the bed nucleus of the stria terminalis (Georges and Aston-Jones, 2001, 2002; Watabe-Uchida et al., 2012). (Inset) KOR abundance in these structures. Heat map color-coded (Red = most abundant) by reported radioligand binding (Mansour et al., 1987; Le Merrer et al., 2009). Amy, amygdala; BST, bed nucleus of the stria terminalis, D1, dopamine receptor D1; D2, dopamine receptor D2; Enk, enkephalin; Hipp, hippocampus; LHb, lateral habenula; mPFC, medial prefrontal cortex; NAc, nucleus accumbens; PPN, pedunculopontine nucleus/pedunculopontine tegmental nucleus; RMTg, rostromedial tegmental nucleus; VP, ventral pallidum; SP, substance P; VTA, ventral tegmental area.