The role of Olfaction in MCH-regulated spontaneous maternal responses

Alhassen, Lamees; Phan, Alvin; Alhassen, Wedad; Nguyen, Paul; Lo, Alice; Shaharuddin, Hanan; Sanathara, Nayna; Civelli, Olivier; Alachkar, Amal

doi:10.1016/j.brainres.2019.05.021

Cited by 21 publications

(35 citation statements)

References 24 publications

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“…MCH is a phylogenetically conserved peptide 13 and has a wide range of functions, although, in the brain, MCH is strongly implicated in the control of motivated behaviours. 8,[16][17][18][19][20][21][22][23] Consequently, MCH expression in the mPOA at late lactation may drive behavioural changes associated with the transition between lactation and weaning, 12,13,29,30,52 Although the present study showed very few colocalisations between VGAT and MCH in the mPOA, suggesting that these neurones are not GABAergic in mice, Rondini et al 8 showed that approximately 94% of neurones expressing MCH mRNA in the mPOA of lactating rats coexpress GAD67 mRNA, another marker of GABAergic cells.…”

Section: Discussioncontrasting

confidence: 46%

“…Although MCH expression is predominantly found in the LHA, previous studies have identified a transitory MCH expression in the preoptic area of rats and mice at the end of lactation. MCH is a phylogenetically conserved peptide and has a wide range of functions, although, in the brain, MCH is strongly implicated in the control of motivated behaviours . Consequently, MCH expression in the mPOA at late lactation may drive behavioural changes associated with the transition between lactation and weaning, particularly the suppression of maternal behaviours .…”

Section: Discussionmentioning

confidence: 99%

“…Melanin‐concentrating hormone‐expressing neurones are mainly found in the lateral hypothalamic area (LHA), incerto‐hypothalamic area and zona incerta . MCH regulates several motivated behaviours, including feeding, aggression, sexual and maternal care . Interestingly, behavioural expression is robustly altered during lactation .…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15] MCH regulates several motivated behaviours, including feeding, aggression, sexual and maternal care. 8,[16][17][18][19][20][21][22][23] Interestingly, behavioural expression is robustly altered during lactation. 1,[24][25][26] For example, lactating animals must increase their food intake to cope with the high energy demands to feed the pups, the dams increase their aggressive behaviour against intruders, sexual behaviour is temporarily inhibited and, evidently, the expression of maternal behaviour is robustly induced.…”

mentioning

confidence: 99%

“…1,[24][25][26] For example, lactating animals must increase their food intake to cope with the high energy demands to feed the pups, the dams increase their aggressive behaviour against intruders, sexual behaviour is temporarily inhibited and, evidently, the expression of maternal behaviour is robustly induced. 1,[24][25][26][27] Noteworthy, some key behaviours altered during lactation are also influenced by MCH, [16][17][18][19][20][21][22][23] suggesting that the temporary expression of MCH in the mPOA plays a role in the transition between lactation and weaning. Accordingly, mPOA neurones densely innervate hypothalamic nuclei that control reproduction and sexual behaviour.…”

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confidence: 99%

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Regulation and neurochemical identity of melanin‐concentrating hormone neurones in the preoptic area of lactating mice

Teixeira

Wasinski

Lima

et al. 2019

J Neuroendocrinology

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Neurones expressing the melanin‐concentrating hormone (MCH) can be found in the medial preoptic area (mPOA) and ventral aspects of the periventricular preoptic nucleus of rats by mid‐to‐late lactation and this expression disappears after weaning. The transitory expression of MCH in the preoptic area suggests a role for these neurones in the control of the end of lactation. However, the neurochemical identity of mPOA MCH neurones and the regulatory factors that control the transient MCH expression remain largely unknown, especially in the mouse. In the present study, we showed that mice also present the transitory expression of MCH in the mPOA at late lactation. mPOA MCH cells did not colocalise significantly with markers of GABAergic (VGAT), glutamatergic (VGLUT2 and VGLUT3) or dopaminergic (tyrosine hydroxylase) neurones. mPOA MCH cells also did not express Kiss1 or oxytocin. By contrast, approximately 70% and 90% of mPOA MCH neurones colocalised with oestrogen receptor α and prolactin‐induced phosphorylated signal transducer and activator of transcription 5 (STAT5), respectively. Finally, we demonstrated that the number of MCH neurones in the mPOA is significantly higher in females during the first lactation, compared to mice on the second lactation or pregnant mice during the first lactation or brain‐specific STAT5 knockout mice during the first lactation. In summary, our findings indicate that MCH neurones in the mPOA of lactating mice are sensitive to oestrogens and prolactin. Thus, mPOA MCH expression is possibly influenced by hormonal variations. Furthermore, the STAT5 signalling pathway is likely involved in the regulation of MCH expression in the mPOA of lactating mice.

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Section: Discussioncontrasting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation and neurochemical identity of melanin‐concentrating hormone neurones in the preoptic area of lactating mice

Teixeira

Wasinski

Lima

et al. 2019

J Neuroendocrinology

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An N‐terminal fusion allele to study melanin concentrating hormone receptor 1

Jasso

Kamba

Zimmerman

et al. 2021

Genesis

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Cilia on neurons play critical roles in both the development and function of the central nervous system (CNS). While it remains challenging to elucidate the precise roles for neuronal cilia, it is clear that a subset of G‐protein‐coupled receptors (GPCRs) preferentially localize to the cilia membrane. Further, ciliary GPCR signaling has been implicated in regulating a variety of behaviors. Melanin concentrating hormone receptor 1 (MCHR1), is a GPCR expressed centrally in rodents known to be enriched in cilia. Here we have used MCHR1 as a model ciliary GPCR to develop a strategy to fluorescently tag receptors expressed from the endogenous locus in vivo. Using CRISPR/Cas9, we inserted the coding sequence of the fluorescent protein mCherry into the N‐terminus of Mchr1. Analysis of the fusion protein (mCherryMCHR1) revealed its localization to neuronal cilia in the CNS, across multiple developmental time points and in various regions of the adult brain. Our approach simultaneously produced fortuitous in/dels altering the Mchr1 start codon resulting in a new MCHR1 knockout line. Functional studies using electrophysiology show a significant alteration of synaptic strength in MCHR1 knockout mice. A reduction in strength is also detected in mice homozygous for the mCherry insertion, suggesting that while the strategy is useful for monitoring the receptor, activity could be altered. However, both lines should aid in studies of MCHR1 function and contribute to our understanding of MCHR1 signaling in the brain. Additionally, this approach could be expanded to aid in the study of other ciliary GPCRs.

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Ciliary melanin‐concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex‐independent manner

Diniz

Battagello

Klein

et al. 2020

J of Neuroscience Research

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Melanin‐concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein‐coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a subcellular structure called the primary cilium, which has been associated, among other functions, with the detection of free neurochemical messengers present in the extracellular space. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, midbrain areas, and in the spinal cord. No differences were observed between male and female mice, and interspecies differences were found in the caudate‐putamen nucleus and the subgranular zone. Ciliary MCHR1 was found in close association with several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin‐releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicate that nonsynaptic communication plays a prominent role in the normal function of the MCH system.

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The role of Olfaction in MCH-regulated spontaneous maternal responses

Cited by 21 publications

References 24 publications

Regulation and neurochemical identity of melanin‐concentrating hormone neurones in the preoptic area of lactating mice

Regulation and neurochemical identity of melanin‐concentrating hormone neurones in the preoptic area of lactating mice

An N‐terminal fusion allele to study melanin concentrating hormone receptor 1

Ciliary melanin‐concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex‐independent manner

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