Lateral Hypothalamic Mc3R-Expressing Neurons Modulate Locomotor Activity, Energy Expenditure, and Adiposity in Male Mice

Pei, Hongjuan; Patterson, Christa M.; Sutton, Amy K.; Burnett, Korri H.; Myers, Martin G.; Olson, David P.

doi:10.1210/en.2018-00747

Cited by 24 publications

(26 citation statements)

References 64 publications

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“…The specificity of Cre expression in MC3R‐expressing neurons of MC3R Cre mice was previously confirmed in the arcuate nucleus, ventromedial nucleus and the lateral hypothalamus (Pei et al . ). We extended this study and also tested the specificity of Cre expression in the VTA using RNAscope ISH in MC3R Cre mice.…”

Section: Resultsmentioning

confidence: 97%

“…These mice were generated by crossing mice expressing Cre recombinase in MC3R neurons ( MC3R Cre ) (Pei et al . ) with a Cre inducible EYFP mouse line (Fig. A ).…”

Section: Resultsmentioning

confidence: 99%

“…The specificity of Cre expression in MC3R neurons was confirmed previously in a separate study describing the creation and validation of this mouse (Pei et al . ). In total, 84 neurons from 60 mice were used in the experiments described in the present study.…”

Section: Methodsmentioning

confidence: 97%

“…Male and female transgenic mice expressing EYFP in MC3R neurons (5-14 weeks old, 20-25 g, fed ad libitum) on a mixed C57/129 background were used in all experiments. Mice were generated by crossing transgenic mice expressing Cre recombinase tethered to the MC3R gene product by a 2A-self-cleaving peptide (Pei et al 2018) (generously provided by Dr David P. Olson, University of Michigan, Ann Arbor, MI, USA) with a Cre inducible EYFP Ai3 transgenic mouse line from The Jackson Laboratory (Bar Harbor, ME, USA) (Stock # 007903). The specificity of Cre expression in MC3R neurons was confirmed previously in a separate study describing the creation and validation of this mouse (Pei et al 2018).…”

Section: Animalsmentioning

confidence: 99%

“…RNAscope ISH was performed as described previously (Pei et al 2018). Briefly, adult mice were quickly decapitated under anaesthesia.…”

Section: Rnascope In Situ Hybridization (Ish) Assaymentioning

confidence: 99%

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Alpha‐melanocyte stimulating hormone increases the activity of melanocortin‐3 receptor‐expressing neurons in the ventral tegmental area

West

Lü

Olson

et al. 2019

The Journal of Physiology

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Key points Alpha‐melanocyte stimulating hormone (α‐MSH) is an anorexigenic peptide. Injection of the α‐MSH analog MTII into the ventral tegmental area (VTA) decreases food and sucrose intake and food reward. Melanocortin‐3 receptors (MC3R) are highly expressed in the VTA, suggesting that the effects of intra‐VTA α‐MSH may be mediated by α‐MSH changing the activity of MC3R‐expressing VTA neurons. α‐MSH increased the firing rate of MC3R VTA neurons in acute brain slices from mice, although it did not affect the firing rate of non‐MC3R VTA neurons. The α‐MSH induced increase in MC3R neuron firing rate is probably activity‐dependent, and was independent of fast synaptic transmission and intracellular Ca2+ levels. These results help us to better understand how α‐MSH acts in the VTA to affect feeding and other dopamine‐dependent behaviours. Abstract The mesocorticolimbic dopamine system, the brain's reward system, regulates multiple behaviours, including food intake and food reward. There is substantial evidence that the melanocortin system of the hypothalamus, an important neural circuit controlling feeding and body weight, interacts with the mesocorticolimbic dopamine system to affect feeding, food reward and body weight. For example, melanocortin‐3 receptors (MC3Rs) are expressed in the ventral tegmental area (VTA) and our laboratory previously showed that intra‐VTA injection of the MC3R agonist, MTII, decreases home‐cage food intake and operant responding for sucrose pellets. However, the cellular mechanisms underlying the effects of intra‐VTA alpha‐melanocyte stimulating hormone (α‐MSH) on feeding and food reward are unknown. To determine how α‐MSH acts in the VTA to affect feeding, we performed electrophysiological recordings in acute brain slices from mice expressing enhanced yellow fluorescent protein in MC3R neurons to test how α‐MSH affects the activity of VTA MC3R neurons. α‐MSH significantly increased the firing rate of VTA MC3R neurons without altering the activity of non‐MC3R expressing VTA neurons. In addition, the α‐MSH‐induced increase in MC3R neuron activity was independent of fast synaptic transmission and intracellular Ca2+ levels. Finally, we show that the effect of α‐MSH on MC3R neuron firing rate is probably activity‐dependent. Overall, these studies provide an important advancement in the understanding of how α‐MSH acts in the VTA to affect feeding and food reward.

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Section: Resultsmentioning

confidence: 97%

“…These mice were generated by crossing mice expressing Cre recombinase in MC3R neurons ( MC3R Cre ) (Pei et al . ) with a Cre inducible EYFP mouse line (Fig. A ).…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 97%

Section: Animalsmentioning

confidence: 99%

“…RNAscope ISH was performed as described previously (Pei et al 2018). Briefly, adult mice were quickly decapitated under anaesthesia.…”

Section: Rnascope In Situ Hybridization (Ish) Assaymentioning

confidence: 99%

See 3 more Smart Citations

Alpha‐melanocyte stimulating hormone increases the activity of melanocortin‐3 receptor‐expressing neurons in the ventral tegmental area

West

Lü

Olson

et al. 2019

The Journal of Physiology

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Whole‐brain efferent and afferent connectivity of mouse ventral tegmental area melanocortin‐3 receptor neurons

Dunigan

Swanson

Olson

et al. 2020

J of Comparative Neurology

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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.

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Organization of neural systems expressing melanocortin‐3 receptors in the mouse brain: Evidence for sexual dimorphism

Bedenbaugh

Brener

Maldonado

et al. 2022

J of Comparative Neurology

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The central melanocortin system is fundamentally important for controlling food intake and energy homeostasis. Melanocortin-3 receptor (MC3R) is one of two major receptors of the melanocortin system found in the brain. In contrast to the well-characterized melanocortin-4 receptor (MC4R), little is known regarding the organization of MC3R-expressing neural circuits. To increase our understanding of the intrinsic organization of MC3R neural circuits, identify specific differences between males and females, and gain a neural systems level perspective of this circuitry, we conducted a brain-wide mapping of neurons labeled for MC3R and characterized the distribution of their projections. Analysis revealed MC3R neuronal and terminal

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Lateral Hypothalamic Mc3R-Expressing Neurons Modulate Locomotor Activity, Energy Expenditure, and Adiposity in Male Mice

Cited by 24 publications

References 64 publications

Alpha‐melanocyte stimulating hormone increases the activity of melanocortin‐3 receptor‐expressing neurons in the ventral tegmental area

Alpha‐melanocyte stimulating hormone increases the activity of melanocortin‐3 receptor‐expressing neurons in the ventral tegmental area

Whole‐brain efferent and afferent connectivity of mouse ventral tegmental area melanocortin‐3 receptor neurons

Organization of neural systems expressing melanocortin‐3 receptors in the mouse brain: Evidence for sexual dimorphism

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