An anatomic basis for the communication of hypothalamic, cortical and mesolimbic circuitry in the regulation of energy balance

Central neural control of complex feeding behaviour is likely to be influenced by a number of factors including homeostatic responses to peripheral nutrient status, cortical integration of feeding-related cues and the underlying reward value of food. We have used retrogradely transported neurotropic viruses, as tools to map chains of synaptically-connected neurons, in conjunction with neurochemical markers of feeding-related peptides to expand the blueprint of the circuitries that underlie these different components of feeding behaviour. We have identified projections to insular and anterior cingulate cortex, extending from the arcuate nucleus through synaptic relays in the lateral hypothalamic area and midline thalamic nuclei. Cortically projecting neurons from the hypothalamic arcuate nucleus were found predominantly in its lateral aspects and contained anorexigenic peptides with no representation amongst more medially-positioned neurons containing orexigenic peptides. Largely overlapping pathways were shown to project multisynaptically to the shell of the nucleus accumbens but those with origins in the arcuate nucleus had either orexigenic or anorexigenic phenotypes. Similar to the cortical projections, those relaying to the nucleus accumbens in the lateral hypothalamus contained the orexigenic peptides orexin-A and melanin-concentrating hormone in similar to 30% of cases. Common to the neural pathways directed to all three virally-injected areas were nodes of synaptic relays in the lateral hypothalamus and midline thalamic nuclei. These regions are well positioned to integrate sensory information about energy homeostasis and the reward value of food in the passage of this information to the 'ingestive cortex'.