Figure 4.

Schematic representation of the possible circuits involved in the control of mesoaccumbens DA neurons by mPFC 5-HT_2CR. In the mPFC, the 5-HT_2CR is expressed on GABA interneurons as well as on pyramidal glutamate neurons (Liu et al., 2007; Visokanov et al., 1998). The majority of pyramidal glutamate neurons do not provide direct innervation to mesoaccumbens DA neurons in either the VTA or the NAc (Sesack et al., 2003; Omelchenko and Sesack, 2007). Within the mesoaccumbens system, GABAergic neurons provide an inhibitory interface between glutamate input and mesoaccumbens DA neurons. (1) Stimulation of 5-HT_2CR on GABA interneurons would function to reduce excitatory glutamate output to the mesoaccumbens DA pathway, thereby leading to an increase in DA neuron activity consequent to reduced GABA transmission within the VTA and/or NAc. (2) Stimulation of 5-HT_2CR on pyramidal cells would increase excitatory glutamate output, thereby increasing GABA transmission within the VTA and/or NAc and, consequently, decreasing DA neuron activity. (3) Activation of pyramidal neurons could also provide indirect control of the mesoaccumbens DA pathway via other brain regions (amygdala, mediodorsal nucleus of the thalamus, lateral hypothalamus, brainstem laterodorsal/peduncolopontine tegmentum, dorsal raphe nucleus) receiving input from the mPFC pyramidal neurons (Gabbott et al., 2005; Sesack et al., 2003), and innervating the VTA and/or the NAc (Azmitia and Segal, 1978; Geisler et al., 2007; Omelchenko and Sesack, 2007; Pinto et al., 2003; Sesack et al., 2003). DA= dopamine; mPFC= medial prefrontal cortex; VTA= ventral tegmental area; NAc= nucleus accumbens; Pyr= pyramidal neuron; Glu= glutamate.