Functional heterogeneity of POMC neurons relies on mTORC1 signaling

Saucisse, Nicolas; Mazier, Wilfrid; Simon, Vincent; Binder, Elke; Catania, Caterina; Bellocchio, Luigi; Romanov, Roman A.; Léon, Stéphane; Matías, Isabelle; Zizzari, Philippe; Quarta, Carmelo; Cannich, Astrid; Meece, Kana; Gonzales, Delphine; Clark, Samantha; Becker, Julia; Yeo, Giles S.H.; Fioramonti, Xavier; Merkle, Florian T.; Wardlaw, Sharon L.; Harkany, Tibor; Massa, Federico; Marsicano, Giovanni; Cota, Daniela

doi:10.1016/j.celrep.2021.109800

Cited by 28 publications

(13 citation statements)

References 71 publications

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“…Acute inhibition of mTORC1 activity after optogenetic activation of POMC neurons reduced POMC/GABAergic transmission and increased POMC/glutamatergic transmission at the same time. This study indicates the heterogeneity of POMC function relies on mTORC1 signaling, which makes POMC neurons regulate appetite bidirectionally ( 69 ).…”

Section: Optogenetic Findings In Depressive-like Behaviorsmentioning

confidence: 89%

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms

Shi

Du²,

Xia³

et al. 2022

Front. Psychiatry

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BackgroundsThe neural circuit mechanisms underlying depression remain unclear. Recently optogenetics has gradually gained recognition as a novel technique to regulate the activity of neurons with light stimulation. Scientists are now transferring their focus to the function of brain regions and neural circuits in the pathogenic progress of depression. Deciphering the circuitry mechanism of depressive-like behaviors may help us better understand the symptomatology of depression. However, few studies have summarized current progress on optogenetic researches into the neural circuit mechanisms of depressive-like behaviors.AimsThis review aimed to introduce fundamental characteristics and methodologies of optogenetics, as well as how this technique achieves specific neuronal control with spatial and temporal accuracy. We mainly summarized recent progress in neural circuit discoveries in depressive-like behaviors using optogenetics and exhibited the potential of optogenetics as a tool to investigate the mechanism and possible optimization underlying antidepressant treatment such as ketamine and deep brain stimulation.MethodsA systematic review of the literature published in English mainly from 2010 to the present in databases was performed. The selected literature is then categorized and summarized according to their neural circuits and depressive-like behaviors.ConclusionsMany important discoveries have been made utilizing optogenetics. These findings support optogenetics as a powerful and potential tool for studying depression. And our comprehension to the etiology of depression and other psychiatric disorders will also be more thorough with this rapidly developing technique in the near future.

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Section: Optogenetic Findings In Depressive-like Behaviorsmentioning

confidence: 89%

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms

Shi

Du²,

Xia³

et al. 2022

Front. Psychiatry

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“…An increased β-endorphin release has been suggested to mediate hyperphagia caused by cannabinoid receptors in POMC neurons 66 . POMC neuron heterogeneity may be speculated to explain inconsistent roles of POMC neurons in body weight 45 , 46 , 67 . The POMC neuron-mediated melanocortin action is still widely perceived to produce negative energy balance 37 .…”

Section: Discussionmentioning

confidence: 99%

“…Given the known heterogeneity of POMC neurons [45][46][47] , no changes in body weight by chronic activation of POMC neurons may be due to non-melanocortin actions. To address this possibility, we next aimed to further examine the impact of POMC melanocortin gain of function.…”

Section: Overexpression Of α-Msh In Pomc Neurons Fails To Reduce Body...mentioning

confidence: 99%

The melanocortin action is biased toward protection from weight loss in mice

Liu

Jiang

et al. 2023

Nat Commun

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The melanocortin action is well perceived for its ability to regulate body weight bidirectionally with its gain of function reducing body weight and loss of function promoting obesity. However, this notion cannot explain the difficulty in identifying effective therapeutics toward treating general obesity via activation of the melanocortin action. Here, we provide evidence that altered melanocortin action is only able to cause one-directional obesity development. We demonstrate that chronic inhibition of arcuate neurons expressing proopiomelanocortin (POMC) or paraventricular hypothalamic neurons expressing melanocortin receptor 4 (MC4R) causes massive obesity. However, chronic activation of these neuronal populations failed to reduce body weight. Furthermore, gain of function of the melanocortin action through overexpression of MC4R, POMC or its derived peptides had little effect on obesity prevention or reversal. These results reveal a bias of the melanocortin action towards protection of weight loss and provide a neural basis behind the well-known, but mechanistically ill-defined, predisposition to obesity development.

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“…In addition to POMC products, POMC neurons can also release neurotransmitters including glutamate and GABA [ 46 ]. Importantly, activation of cannabinoid receptor 1 (CB1R) in POMC neurons can promote feeding by increasing the release of β-endorphin [ 47 ] and GABA [ 48 ], which is opposite to the classic anorexic role of POMC neurons. So far, bidirectional functions of POMC neurons on energy expenditure and physical activity are not reported.…”

Section: Discussionmentioning

confidence: 99%

SK3 in POMC neurons plays a sexually dimorphic role in energy and glucose homeostasis

Bean

Liu

et al. 2022

Cell Biosci

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Background Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood. Results We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females. Conclusion These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons.

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Functional heterogeneity of POMC neurons relies on mTORC1 signaling

Cited by 28 publications

References 71 publications

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms

The melanocortin action is biased toward protection from weight loss in mice

SK3 in POMC neurons plays a sexually dimorphic role in energy and glucose homeostasis

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