Galanin neurons in the medial preoptic area govern parental behaviour

Zheng, Wu; Autry, Anita E.; Bergan, Joseph F; Watabe-Uchida, Mitsuko; Dulac, Catherine

doi:10.1038/nature13307

Cited by 501 publications

(702 citation statements)

References 54 publications

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“…This might be mediated by prolactin itself but also by the closely related placental lactogens that act on the Prlr and are elevated in the blood throughout the second half of pregnancy (25). Importantly, unlike some recent reports that have used cell ablation approaches (26,27) or blockade of neurotransmitter production (28,29) to identify critical cell types mediating maternal behavior, in this model, the neuronal circuitry is completely intact. The profound deficit arises specifically from the lack of appropriate hormonal input into these circuits.…”

Section: Discussionmentioning

confidence: 97%

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

Brown

Aoki

Ladyman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

127

147

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Pregnancy hormones, such as prolactin, sensitize neural circuits controlling parental interactions to induce timely activation of maternal behaviors immediately after parturition. While the medial preoptic area (MPOA) is known to be critical for maternal behavior, the specific role of prolactin in this brain region has remained elusive. Here, we evaluated the role of prolactin action in the MPOA using complementary genetic strategies in mice. We characterized prolactin-responsive neurons within the MPOA at different hormonal stages and delineated their projections in the brain. We found that MPOA neurons expressing prolactin receptors (Prlr) form the nexus of a complex prolactin-responsive neural circuit, indicating that changing prolactin levels can act at multiple sites and thus, impinge on the overall activity of a distributed network of neurons. Conditional KO of Prlr from neuronal subpopulations expressing the neurotransmitters GABA or glutamate within this circuit markedly reduced the capacity for prolactin action both in the MPOA and throughout the network. Each of these manipulations, however, produced only subtle impacts on maternal care, suggesting that this distributed circuit is robust with respect to alterations in prolactin signaling. In contrast, acute deletion of Prlr in all MPOA neurons of adult female mice resulted in profound deficits in maternal care soon after birth. All mothers abandoned their pups, showing that prolactin action on MPOA neurons is necessary for the normal expression of postpartum maternal behavior in mice. Our data establish a critical role for prolactin-induced behavioral responses in the maternal brain, ensuring survival of mammalian offspring.maternal behavior | prolactin | prolactin receptor | medial preoptic area M aternal care is critical to survival of dependent offspring in mammals. Seminal work from Rosenblatt (1), published 50 y ago, showed that maternal behavior can be exhibited in ovariectomized, hypophysectomized rats, suggesting an underlying neural basis that was not dependent on hormonal inputs. Subsequent studies have characterized a complex neural circuitry controlling parental interactions (2, 3), with distributed sites mediating different components of the behavior (4). While the neural circuit controlling maternal behavior is not thought to be dependent on hormonal inputs, it is clear that pregnancy hormones, particularly rising levels of estradiol, oxytocin, prolactin, and placental lactogen, coupled with an abrupt decrease in progesterone can sensitize the underlying circuitry to induce timely activation of maternal behaviors immediately after parturition (5). The medial preoptic area (MPOA) forms a critical nexus (2, 3), integrating a range of hormonal and sensory inputs into the maternal circuit.Within the complex hormonal milieu of pregnancy, the specific role of prolactin in maternal behavior has remained elusive. This is largely because prolactin and the related placental lactogen have an obligate role in sustaining ovarian progesterone productio...

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Section: Discussionmentioning

confidence: 97%

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

Brown

Aoki

Ladyman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

127

147

View full text Add to dashboard Cite

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“…This organization is further manifested in the brain: some brain areas and neuron types contribute to the control of an entire suite of related behaviours, while other neurons control the execution of specific behaviours. For example, galanin neurons in the medial preoptic area of the hypothalamus are essential for multiple components of parental care 33 , and more discrete neuronal types likely control the execution of each component. However, it is unknown how this hierarchical organization is manifested at the genetic level.…”

Section: Discussionmentioning

confidence: 99%

The genetic basis of parental care evolution in monogamous mice

Bendesky

Kwon

Lassance

et al. 2017

Nature

233

202

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Summary Parental care is essential for the survival of mammals, yet the mechanisms underlying its evolution remain largely unknown. Here we show that two sister species of mice, Peromyscus polionotus and P. maniculatus, have large and heritable differences in parental behaviour. Using quantitative genetics, we identify 12 genomic regions that affect parental care, eight of which have sex-specific effects, suggesting that parental care can evolve independently in males and females. Furthermore, some regions affect parental care broadly, whereas others affect specific behaviours, such as nest building. Of the genes linked to differences in nest-building behaviour, vasopressin is differentially expressed in the hypothalamus of the two species, with increased levels associated with less nest building. Using pharmacology in Peromyscus and chemogenetics in Mus, we show that vasopressin inhibits nest building but not other parental behaviours. Together, our results indicate that variation in an ancient neuropeptide contributes to interspecific differences in parental care.

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“…Physiological mechanical loading can restore the biochemical properties of both tissues, while underloading and overloading reduce tissue function (Gawri et al, 2014;Setton and Chen, 2006;Verteramo and Seedhom, 2007;Wang et al, 2013). ECM turnover is regulated by MMPs and ADAMTS and it is affected by age and degeneration, as the ability of cartilaginous tissues to maintain the ECM declines when both factors increase (Francuski et al, 2014;Illien-Junger et al, 2010;Le Maitre et al, 2004;Molinos et al, 2015;Pauli et al, 2011;Sztrolovics et al, 1997;Wuertz et al, 2009;Yin and Xia, 2014). The effect of osmolarity on the turnover of articular cartilage and IVD ECM is well documented (Amin et al, 2011;Ishihara et al, 1997;Johnson et al, 2014;Wuertz et al, 2007).…”

Section: Trp Channels In Joint Diseasesmentioning

confidence: 99%

The role of transient receptor potential channels in joint diseases

Krupková

Zvick²,

Wuertz‐Kozak³

2017

eCM

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Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous as well as exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca 2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation as well as activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells and the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.

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Galanin neurons in the medial preoptic area govern parental behaviour

Cited by 501 publications

References 54 publications

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

The genetic basis of parental care evolution in monogamous mice

The role of transient receptor potential channels in joint diseases

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