Whole‐brain efferent and afferent connectivity of mouse ventral tegmental area melanocortin‐3 receptor neurons. Issue 6 (10th September 2020)

• Record Type: Journal Article
• Authors: Dunigan, Anna I.; Swanson, Andrew M.; Olson, David P.; Roseberry, Aaron G.
• Is Part Of: Journal of comparative neurology. Volume 529:Issue 6(2021)
• Page Start: 1157
• Page End: 1183
• Publication Date: 2020-09-10
• Subjects: AgRP -- arcuate nucleus -- dopamine -- MC3R -- melanocortin -- monosynaptic rabies -- POMC -- RRID Addgene_71760 -- VTA; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.25013
• Languages: English
• ISSNs: 0021-9967

Abstract

Abstract: The mesolimbic dopamine (DA) system is involved in the regulation of multiple behaviors, including feeding, and evidence demonstrates that the melanocortin system can act on the mesolimbic DA system to control feeding and other behaviors. The melanocortin‐3 receptor (MC3R) is an important component of the melanocortin system, but its overall role is poorly understood. Because MC3Rs are highly expressed in the ventral tegmental area (VTA) and are likely to be the key interaction point between the melanocortin and mesolimbic DA systems, we set out to identify both the efferent projection patterns of VTA MC3R neurons and the location of the neurons providing afferent input to them. VTA MC3R neurons were broadly connected to neurons across the brain but were strongly connected to a discrete set of brain regions involved in the regulation of feeding, reward, and aversion. Surprisingly, experiments using monosynaptic rabies virus showed that proopiomelanocortin (POMC) and agouti‐related protein (AgRP) neurons in the arcuate nucleus made few direct synapses onto VTA MC3R neurons or any of the other major neuronal subtypes in the VTA, despite being extensively labeled by general retrograde tracers injected into the VTA. These results greatly contribute to our understanding of the anatomical interactions between the melanocortin and mesolimbic systems and provide a foundation for future studies of VTA MC3R neurons and the circuits containing them in the control of feeding and other behaviors. Abstract : VTA MC3R neurons are a likely site of interaction between homeostatic and hedonic feeding circuits. VTA MC3R neurons send efferent projections to, and receive afferent input from, multiple brain regions involved in feeding, reward, and aversion. Very few POMC and AgRP neurons were labeled by monosynaptic rabies from multiple VTA neuron subtypes.