MCH Neuron Activity Is Sufficient for Reward and Reinforces Feeding

Dilsiz, Pelin; Aklan, İltan; Atasoy, Nilüfer Sayar; Yavuz, Yavuz; Filiz, Gizem; Köksalar, Fulya; Ateş, Tayfun; Öncül, Merve; Çoban, İlknur; Oz, Edanur Ates; Cebecioğlu, Utku; İkbal, Muhammed; Yılmaz, Bayram; Atasoy, Deniz

doi:10.1159/000501234

Cited by 44 publications

(31 citation statements)

References 39 publications

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“…The strains also have nearly identical penetrance and specificity (Kong et al, 2010;Jego et al, 2013). Ultimately, we chose to focus on the Tg(Pmch-cre)1Lowl/J line because it is used and cited more frequently, making our findings applicable to more researchers in the field (Kong et al, 2010;Varin et al, 2018;Dilsiz et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Dissociated Pmch and Cre Expression in Lactating Pmch-Cre BAC Transgenic Mice

et al. 2020

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The melanin-concentrating hormone (MCH) system plays a role in many physiological processes including reproduction and lactation. However, research regarding the function of MCH on different aspects of the reproductive function lags, due in part to a lack of validated genetic models with which to interrogate the system. This is particularly true in the case of female reproduction, as the anatomy and function of the MCH system is not well-characterized in the female mouse. We set out to determine whether the commercially available Pmch-Cre transgenic mouse line is a viable model to study the role of MCH neurons in distinct female reproductive states. We found that Pmch is transiently expressed in several nuclei of the rostral forebrain at the end of lactation. This includes the medial subdivision of the medial preoptic nucleus, the paraventricular nucleus of the hypothalamus, the ventral subdivision of the lateral septum, the anterodorsal preoptic nucleus and the anterodorsal nucleus of the thalamus. The Pmch expression in these sites, however, does not reliably induce Cre expression in the Pmch-Cre (BAC) transgenic mouse, making this line an inadequate model with which to study the role of MCH in behavioral and/or neuroendocrine adaptations of lactation. We also contribute to the general knowledge of the anatomy of the murine MCH system by showing that lactation-induced Pmch expression in the rostral forebrain is mostly observed in GABAergic (VGAT) neurons, in contrast to the typical MCH neurons of the tuberal and posterior hypothalamus which are glutamatergic (VGLUT2).

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Section: Discussionmentioning

confidence: 99%

Dissociated Pmch and Cre Expression in Lactating Pmch-Cre BAC Transgenic Mice

et al. 2020

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“…The previous results on the effect of MCH on locomotor activity are mixed. Some report that activation of MCH neurons impairs locomotor activity (Hausen et al, 2016; Zhou et al, 2005), while others report no evident locomotor effect of MCH (Dilsiz et al, 2019; Kela et al, 2003; Sanchez et al, 1997). Some factors may contribute to the inconsistent results, such as the methods used to activate MCH neurons or locomotor testing phase.…”

Section: Discussionmentioning

confidence: 99%

Melanin-concentrating hormone in rat nucleus accumbens or lateral hypothalamus differentially impacts morphine and food seeking behaviors

et al. 2020

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Background: Identifying neural substrates that are differentially affected by drugs of abuse and natural rewards is key to finding a target for an efficacious treatment for substance abuse. Melanin-concentrating hormone is a polypeptide with an inhibitory effect on the mesolimbic dopamine system. Here we test the hypothesis that melanin-concentrating hormone in the lateral hypothalamus and nucleus accumbens shell is differentially involved in the regulation of morphine and food-rewarded behaviors. Methods: Male Sprague–Dawley rats were trained with morphine (5.0 mg/kg, subcutaneously) or food pellets (standard chow, 10–14 g) to induce a conditioned place preference, immediately followed by extinction training. Melanin-concentrating hormone (1.0 µg/side) or saline was infused into the nucleus accumbens shell or lateral hypothalamus before the reinstatement primed by morphine or food, and locomotor activity was simultaneously monitored. As the comparison, melanin-concentrating hormone was also microinjected into the nucleus accumbens shell or lateral hypothalamus before the expression of food or morphine-induced conditioned place preference. Results: Microinfusion of melanin-concentrating hormone into the nucleus accumbens shell (but not into the lateral hypothalamus) prevented the reinstatement of morphine conditioned place preference but had no effect on the reinstatement of food conditioned place preference. In contrast, microinfusion of melanin-concentrating hormone into the lateral hypothalamus (but not in the nucleus accumbens shell) inhibited the reinstatement of food conditioned place preference but had no effect on the reinstatement of morphine conditioned place preference. Conclusions: These results suggest a clear double dissociation of melanin-concentrating hormone in morphine/food rewarding behaviors and melanin-concentrating hormone in the nucleus accumbens shell. Melanin-concentrating hormone could be a potential target for therapeutic intervention for morphine abuse without affecting natural rewards.

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“…In parallel, optogenetic and DREADD stimulation of the MCH neurons and IDTR-dependent ablation of MCH neurons allowed for exploring the role of MCH neurons. Optogenetics and DREADD technologies have also been previously used to explore MCH neurons' role in sleep, reward, and feeding (Blanco-Centurion et al, 2016;Dilsiz et al, 2020;Naganuma et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Brain Primary Cilia Length By MCH Signaling: Evidence From Pharmacological, Genetic, Optogenetic And Chemogenic Manipulations

Alhassen

Kobayashi

et al. 2021

Preprint

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The melanin-concentrating hormone (MCH) system is involved in numerous functions, including energy homeostasis, food intake, sleep, stress, mood, aggression, reward, maternal behavior, social behavior, and cognition. MCH acts on a G protein-coupled receptor MCHR1, which expresses ubiquitously in the brain and localizes to neuronal primary cilia. Cilia act as cells' antennas and play crucial roles in cell signaling to detect and transduce external stimuli to regulate cell differentiation and migration. Cilia are highly dynamic in terms of their length and morphology; however, it is not known if cilia length is causally regulated by MCH system activation in-vivo. In the current work, we examined the effects of activation and inactivation of MCH system on cilia lengths by using different methodologies, including pharmacological (MCHR1 agonist and antagonist GW803430), germline and conditional genetic deletion of MCHR1 and MCH, optogenetic, and chemogenetic (Designer Receptors Exclusively Activated by Designer Drugs (DREADD)) approaches. We found that stimulation of MCH system either directly through MCHR1 activation, or indirectly through optogenetic and chemogenetic-mediated excitation of MCH neurons, causes cilia shortening. In contrast, inactivation of MCH signaling through pharmacological MCHR1 blockade or through genetic manipulations - germline deletion of MCHR1 and conditional ablation of MCH neurons - induces cilia lengthening. Our study is the first to uncover the causal effects of the MCH system in the regulation of the length of brain neuronal primary cilia. These findings place MCH system at a unique position in the ciliary signaling in physiological and pathological conditions, and implicate cilia MCHR1 as a potential therapeutic target for the treatment of pathological conditions characterized by impaired cilia function.

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MCH Neuron Activity Is Sufficient for Reward and Reinforces Feeding

Cited by 44 publications

References 39 publications

Dissociated Pmch and Cre Expression in Lactating Pmch-Cre BAC Transgenic Mice

Dissociated Pmch and Cre Expression in Lactating Pmch-Cre BAC Transgenic Mice

Melanin-concentrating hormone in rat nucleus accumbens or lateral hypothalamus differentially impacts morphine and food seeking behaviors

Regulation of Brain Primary Cilia Length By MCH Signaling: Evidence From Pharmacological, Genetic, Optogenetic And Chemogenic Manipulations

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