Central Melanocortins Regulate the Motivation for Sucrose Reward

Pandit, Rahul; Zwaal, Esther M. van der; Luijendijk, Mieneke C. M.; Brans, Maike A.D.; Rozen, A J van; Ophuis, Ralph J. A. Oude; Vanderschuren, Louk J. M. J.; Adan, Roger A.H.; Fleur, Susanne E. la

doi:10.1371/journal.pone.0121768

Cited by 43 publications

(35 citation statements)

References 48 publications

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“…4). [89][90][91][92][93][94][95] Interestingly, females with ablation of Slc17a6 (vGluT2) specifically in Kiss1 neurons appeared to exhibit a normal ovulatory cycle, an indication that glutamatergic neurotransmission from Kiss1 ARH neurons may not be necessary to support reproductive function. 10 In contrast, complete silencing of Kiss1 ARH neurons in adults 88 produces females with irregular estrus cycles, and the majority of females exhibit persistent diestrus with lower plasma LH levels during diestrus as compared with wild-type controls.…”

Section: Vglut2 Deletion In Kiss1 Neuronsmentioning

confidence: 99%

Arcuate Kisspeptin Neurons Coordinate Reproductive Activities with Metabolism

2019

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Hypothalamic control of fertility is the quintessential homeostatic function. However, fertility is metabolically demanding; so, there must be coordination between energy states and reproductive functions. Because gonadotropin-releasing hormone (GnRH) neurons are devoid of many of the critical metabolic hormone receptors for sensing nutrient levels, it has long been recognized that the sensing of energy stores had to be done by neurons presynaptic to GnRH neurons. Some of the obvious players have been the anorexigenic proopiomelanocortin (POMC) and orexigenic neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, both of which are in close apposition to the median eminence, a circumventricular organ. Indeed, POMC and NPY/AgRP neurons are inversely regulated by glucose and metabolic hormones including insulin and leptin. However, their synaptic connections with GnRH neurons are sparse and/or GnRH neurons are lacking the postsynaptic receptors to mediate the appropriate physiological response. Kisspeptin neurons were discovered in the early part of this century and subsequently shown to project to and control GnRH neuronal excitability. In fact, more recently the arcuate kisspeptin neurons have been identified as the command neurons driving pulsatile release of GnRH. Subsequently, it was shown that arcuate kisspeptin neurons express not only steroid hormone receptors but also metabolic hormone receptors such that similar to POMC neurons, they are excited by insulin and leptin. Therefore, based on the premise that arcuate kisspeptin neurons are the key neurons coordinating energy states with reproduction, we will review not only how these vital neurons control pulsatile GnRH release but how they control energy homeostasis through their synaptic connections with POMC and NPY/AgRP neurons and ultimately how E2 can regulate their excitability.

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Section: Vglut2 Deletion In Kiss1 Neuronsmentioning

confidence: 99%

Arcuate Kisspeptin Neurons Coordinate Reproductive Activities with Metabolism

2019

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“…Likewise, if the POMC 615 neurons are simultaneously activated by the same sensory evidence, then this has an 616 excitatory effect on the same VTA-DA cells, which together with the AgRP disinhibition, 617 provides a means by which VTA-DA signalling can be anchored to updates of predictions on 618 future energetic wealth (i.e., the consequences of beliefs about the current long-term policy 619 are assigned high precision or confidence). This is corroborated by ex-vivo recordings in 620 which VTA-DA neurons increase baseline firing to injections of γ-MSH (Pandit et al 2015). It 621 should be noted that these findings seem to be at odds with the existing consensus that 622 AgRP neurons acts to increase feeding and reward, and MSH acts to decrease feeding (Yen 623 & Roseberry 2015).…”

Section: Interface Between Reward Prediction Errors and Glycaemic Conmentioning

confidence: 81%

The Homeostatic Logic of Reward

Morville

Friston

Burdakov

et al. 2018

Preprint

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17Energy homeostasis depends on behavior to predictively regulate metabolic states within 18 narrow bounds. Here we review three theories of homeostatic control and ask how they 19 provide insight into the circuitry underlying energy homeostasis. We offer two 20 contributions. First, we detail how control theory and reinforcement learning are applied 21 to homeostatic control. We show how these schemes rest on implausible assumptions; 22 either via circular definitions, unprincipled drive functions, or by ignoring environmental 23 volatility. We argue active inference can elude these shortcomings while retaining 24 important features of each model. Second, we review the neural basis of energetic 25 control. We focus on a subset of arcuate subpopulations that project directly to, and are 26 thus in a privileged position to opponently modulate, dopaminergic cells as a function of 27 energetic predictions over a spectrum of time horizons. We discuss how this can be 28 interpreted under these theories, and how this can resolve paradoxes that have arisen. 29 We propose this circuit constitutes a homeostatic-reward interface that underwrites the 30 conjoint optimisation of physiological and behavioural homeostasis. 31 32Keywords. reward prediction error, dopamine, hypothalamus, energy homeostasis, active inference 33. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/242974 doi: bioRxiv preprint first posted online 3 The problem of homeostatic control 34A remarkable feature of physiological systems is their stability. Most physiological 35 variables are regulated within narrow bounds by operational and computational processes 36 collectively known as homeostasis (Cannon 1932). The mechanistic complexity of 37 homeostasis extends beyond simple negative feedback control and embodies a wide 38 spectrum of hierarchically organised physiological control structures, molecule to agent, 39 operating over a multitude of timescales, milliseconds to months (Carpenter 2004). 40Homeostatic control is often framed as the regulation of variables around a fixed set point, 41the achievement of which upholds a physiological equilibrium (Cannon 1932 states to fall within the ranges that afford organismal survival (Fig 1b; Sterling 2012). 55For all motile agents, effective homeostatic control results from the interplay among 56 automated physiological processes (henceforth referred to as physiological homeostasis) 57 . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/242974 doi: bioRxiv preprint first posted online 4 and overt behaviour (henceforth, behavioural homeostasis). The coordinated mechanisms 58 of phys...

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“…We next investigated the identity of CTB‐positive neurons in the Arc that did not express NPY. POMC‐expressing neurons represent another major population of neurons in the Arc, which are a separate from the NPY population, and also project to the VTA (Hahn et al, ; Pandit et al, ). We confirmed that Arc POMC‐immunoreactive neurons project to the VTA, and quantified the Arc POMC projection in the same brains used for NPY tracing (Figure a–c).…”

Section: Resultsmentioning

confidence: 99%

“…We also confirm that Arc POMC neurons project to the VTA (Pandit et al, ). Despite a comparable percentage of VTA‐projecting neurons being NPY and POMC (20–30%), it has to be noted that the absolute number of Arc CTB/POMC neurons is larger than the number of Arc CTB/NPY neurons.…”

Section: Discussionmentioning

confidence: 99%

Afferent neuropeptide Y projections to the ventral tegmental area in normal‐weight male Wistar rats

Gumbs

Vuuregge

Eggels

et al. 2019

J of Comparative Neurology

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The hypothalamic neuropeptide Y (NPY) circuitry is a key regulator of feeding behavior. NPY also acts in the mesolimbic dopaminergic circuitry, where it can increase motivational aspects of feeding behavior through effects on dopamine output in the nucleus accumbens (NAc) and on neurotransmission in the ventral tegmental area (VTA). Endogenous NPY in the NAc originates from local interneurons and afferent projections from the hypothalamic arcuate nucleus (Arc). However, the origin of endogenous NPY in the VTA is unknown. We determined, in normal‐weight male Wistar rats, if the source of VTA NPY is local, and/or whether it is derived from VTA‐projecting neurons. Immunocytochemistry, in situ hybridization and RT‐qPCR were utilized, when appropriate in combination with colchicine treatment or 24 hr fasting, to assess NPY/Npy expression locally in the VTA. Retrograde tracing using cholera toxin beta (CTB) in the VTA, fluorescent immunocytochemistry and confocal microscopy were used to determine NPY‐immunoreactive afferents to the VTA. NPY in the VTA was observed in fibers, but not following colchicine pretreatment. No NPY‐ or Npy‐expressing cell bodies were observed in the VTA. Fasting for 24 hr, which increased Npy expression in the Arc, failed to induce Npy expression in the VTA. Double‐labeling with CTB and NPY was observed in the Arc and in the ventrolateral medulla. Thus, VTA NPY originates from the hypothalamic Arc and the ventrolateral medulla of the brainstem in normal‐weight male Wistar rats. These afferent connections link hypothalamic and brainstem processing of physiologic state to VTA‐driven motivational behavior.

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Central Melanocortins Regulate the Motivation for Sucrose Reward

Cited by 43 publications

References 48 publications

Arcuate Kisspeptin Neurons Coordinate Reproductive Activities with Metabolism

Arcuate Kisspeptin Neurons Coordinate Reproductive Activities with Metabolism

The Homeostatic Logic of Reward

Afferent neuropeptide Y projections to the ventral tegmental area in normal‐weight male Wistar rats

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