Figure 1.

Regulation of food intake relies on multichannel communication between overlapping reward and homeostatic neurocircuits. (a) Schematic diagram of the crosstalk between the homeostatic (hypothalamus, HYP) and reward circuits that control food intake. The HYP is central to energy balance and several of its nuclei are involved in energy regulation [arcuate (ARC), dorsomedial (DMH) ventromedial (VMH) and lateral HYP (LH)] integrating orexigenic and anorexigenic signals from the periphery and the CNS and communicating these to regions from the reward circuitry. For example, orexin neurons in LH are influenced by leptin and ghrelin and, in turn, project to reward regions via OX1 and OX2 receptors. Several key neuropeptides produced in various hypothalamic nuclei are indicated: corticotrophin-releasing hormone (CRH), tyrotrophin-releasing hormone (TRH), oxytocin (OT), vasopressin (AVP), cocaine- and amphetamine-regulated transcript (CART), NPY, agouti-related protein (AgRP), proopiomelanocortin (POMC), galanin (GAL), neurotensin (NT), leptin, orexin, luteinizing hormone-releasing hormone (LHRH) and melanin-concentrating hormone (MCH). By contrast, top-down inhibition of feeding depends heavily on the PFC, including OFC and ACC. The amygdala ascribes emotional attributes and, together with memory and learning circuitry, generates conditioned responses. This circuit is subject to strong influence coming from cortical and mesolimbic input. Many of the orexigenic and anorexigenic peripheral signals directly influence neural computations not only in hypothalamus, but also in mesocorticolimbic structures (amygdala, OFC and hippocampus). Conversely, many classic neurotransmitters (DA, CB, opioids, GABA and serotonin) are produced as a result of mesocorticolimbic activity and influence the HYP. For comprehensive reviews, see [26,105]. (b) Expression of orexigenic and anorexigenic genes in the central circuitry (data derived from the Allen Brain Atlas; http://www.brain-map.org). Each box represents a brain region and the circles indicate expression levels of genes in the region. Circle sizes represent expression density (‘+’ expression is sparse to ‘+++’ expression throughout the entire area). Colors represent expression levels (dark blue < light blue < turquoise < light green < orange < red). The location of each gene symbol in the boxes does not correlate with the distribution of that gene within the brain region it represents. Gene symbols without circles are mentioned when only expression density or level is >0. POMC is a precursor for an orexigen, β-endorphin, and for an anorexigen, α-melanocyte-stimulating hormone. Reproduced, with permission, from [106].