Skip to main content

Advertisement

SpringerLink
Log in

Molecular and functional mapping of the neuroendocrine hypothalamus: a new era begins

  • Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background

Recent advances in neuroscience tools for single-cell molecular profiling of brain neurons have revealed an enormous spectrum of neuronal subpopulations within the neuroendocrine hypothalamus, highlighting the remarkable molecular and cellular heterogeneity of this brain area.

Rationale

Neuronal diversity in the hypothalamus reflects the high functional plasticity of this brain area, where multiple neuronal populations flexibly integrate a variety of physiological outputs, including energy balance, stress and fertility, through crosstalk mechanisms with peripheral hormones. Intrinsic functional heterogeneity is also observed within classically ‘defined’ subpopulations of neuroendocrine neurons, including subtypes with distinct neurochemical signatures, spatial organisation and responsiveness to hormonal cues.

Aim

The aim of this review is to critically evaluate past and current research on the functional diversity of hypothalamic neuroendocrine neurons and their plasticity. It focuses on how this neuronal plasticity in this brain area relates to metabolic control, feeding regulation and interactions with stress and fertility-related neural circuits.

Conclusion

Our analysis provides an original framework for improving our understanding of the hypothalamic regulation of hormone function and the development of neuroendocrine diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

All data cited in this article are publicly available online.

Abbreviations

3V:

Third ventricle

ACTH:

Adrenocorticotropic hormone

AgRP:

Agouti-related protein

ARC:

Arcuate nucleus

AVP:

Arginine vasopressin

AVPV:

Anteroventral periventricular nucleus

CRH:

Corticotropin-releasing hormone

Crhr :

Corticotropin-releasing hormone receptor

DMH:

Dorsal medial hypothalamus

Drd1 :

Dopamine receptor D1

DYN:

Dynorphin

ECM:

Extracellular matrix

ECS:

Extracellular space

ERα:

Oestrogen receptor alpha

FSH:

Follicle-stimulating hormone

GABA:

Gamma-aminobutyric acid

GLP1:

Glucagon-like peptide-1

Glp1r :

Glucagon-like peptide-1 receptor

GnRH:

Gonadotropin hormone-releasing hormone

HFD:

High-fat diet

HPA:

Hypothalamic-pituitary-adrenal axis

HPG:

Hypothalamic-pituitary–gonadal axis

Kiss1:

Kisspeptin

Lepr:

Leptin receptor

LH:

Luteinising hormone

MC4R:

Melanocortin 4 receptor

ME:

Median eminence

mENK:

Methionine enkephalin

MePO:

Median preoptic nucleus

NKB:

Neurokinin B

NPY:

Neuropeptide Y

OV:

Organum vasculosum of the lamina terminalis

OXT:

Oxytocin

Pdyn :

Prodynorphin

POMC:

Proopiomelanocortin

PVN:

Paraventricular nucleus

RCA:

Retrochiasmatic area

Rprm :

Reprimo

SST:

Somatostatin

TH:

Tyrosine hydroxylase

VMH:

Ventral medial hypothalamus

VMHvl:

Ventrolateral division of VMH

αMSH:

Alpha-melanocyte-stimulating hormone

References

  1. Timper K, Bruning JC (2017) Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Dis Model Mech 10(6):679–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zimmerman CA, Leib DE, Knight ZA (2017) Neural circuits underlying thirst and fluid homeostasis. Nat Rev Neurosci 18(8):459–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tran LT, Park S, Kim SK, Lee JS, Kim KW, Kwon O (2022) Hypothalamic control of energy expenditure and thermogenesis. Exp Mol Med 54(4):358–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gautron L, Elmquist JK, Williams KW (2015) Neural control of energy balance: translating circuits to therapies. Cell 161(1):133–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Knepper MA, Kwon TH, Nielsen S (2015) Molecular physiology of water balance. N Engl J Med 372(14):1349–1358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Adamantidis AR, de Lecea L (2023) Sleep and the hypothalamus. Science 382(6669):405–412

    Article  CAS  PubMed  Google Scholar 

  7. Herbison AE (2016) Control of puberty onset and fertility by gonadotropin-releasing hormone neurons. Nat Rev Endocrinol 12(8):452–466

    Article  CAS  PubMed  Google Scholar 

  8. Navarro VM (2020) Metabolic regulation of kisspeptin - the link between energy balance and reproduction. Nat Rev Endocrinol 16(8):407–420

    Article  PubMed  PubMed Central  Google Scholar 

  9. Frankiensztajn LM, Elliott E, Koren O (2020) The microbiota and the hypothalamus-pituitary-adrenocortical (HPA) axis, implications for anxiety and stress disorders. Curr Opin Neurobiol 62:76–82

    Article  CAS  PubMed  Google Scholar 

  10. Agorastos A, Chrousos GP (2022) The neuroendocrinology of stress: the stress-related continuum of chronic disease development. Mol Psychiatry 27(1):502–513

    Article  PubMed  Google Scholar 

  11. Stuber GD (2023) Neurocircuits for motivation. Science 382(6669):394–398

    Article  CAS  PubMed  Google Scholar 

  12. Mei L, Osakada T, Lin D (2023) Hypothalamic control of innate social behaviors. Science 382(6669):399–404

    Article  CAS  PubMed  Google Scholar 

  13. Chen R, Wu X, Jiang L, Zhang Y (2017) Single-cell RNA-seq reveals hypothalamic cell diversity. Cell Rep 18(13):3227–3241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kim DW, Washington PW, Wang ZQ, Lin SH, Sun C, Ismail BT, Wang H, Jiang L, Blackshaw S (2020) The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development. Nat Commun 11(1):4360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Steuernagel L, Lam BYH, Klemm P, Dowsett GKC, Bauder CA, Tadross JA, Hitschfeld TS, Del Rio MA, Chen W, de Solis AJ et al (2022) HypoMap-a unified single-cell gene expression atlas of the murine hypothalamus. Nat Metab 4(10):1402–1419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yu H, Rubinstein M, Low MJ (2022) Developmental single-cell transcriptomics of hypothalamic POMC neurons reveal the genetic trajectories of multiple neuropeptidergic phenotypes. Elife. https://doi.org/10.7554/eLife.72883

    Article  PubMed  PubMed Central  Google Scholar 

  17. Herb BR, Glover HJ, Bhaduri A, Colantuoni C, Bale TL, Siletti K, Hodge R, Lein E, Kriegstein AR, Doege CA, Ament SA (2023) Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus. Sci Adv 9(45):eadf6251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lei Y, Liang X, Sun Y, Yao T, Gong H, Chen Z, Gao Y, Wang H, Wang R, Huang Y et al (2024) Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus. Cell Metab 36(2):438–453

    Article  CAS  PubMed  Google Scholar 

  19. D’Agostino G, Diano S (2010) Alpha-melanocyte stimulating hormone: production and degradation. J Mol Med (Berl) 88(12):1195–1201

    Article  CAS  PubMed  Google Scholar 

  20. Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, Ferreira M, Tang V, McGovern RA, Kenny CD et al (2005) Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123(3):493–505

    Article  CAS  PubMed  Google Scholar 

  21. Williams KW, Elmquist JK (2012) From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nat Neurosci 15(10):1350–1355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lu D, Willard D, Patel IR, Kadwell S, Overton L, Kost T, Luther M, Chen W, Woychik RP, Wilkison WO et al (1994) Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371(6500):799–802

    Article  CAS  PubMed  Google Scholar 

  23. Tong Q, Ye CP, Jones JE, Elmquist JK, Lowell BB (2008) Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci 11(9):998–1000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Atasoy D, Betley JN, Su HH, Sternson SM (2012) Deconstruction of a neural circuit for hunger. Nature 488(7410):172–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, Cone RD, Low MJ (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411(6836):480–484

    Article  CAS  PubMed  Google Scholar 

  26. Andermann ML, Lowell BB (2017) Toward a wiring diagram understanding of appetite control. Neuron 95(4):757–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Quarta C, Fioramonti X, Cota D (2020) POMC neurons dysfunction in diet-induced metabolic disease: hallmark or mechanism of disease? Neuroscience 447:3–14

    Article  CAS  PubMed  Google Scholar 

  28. Grayson BE, Seeley RJ, Sandoval DA (2013) Wired on sugar: the role of the CNS in the regulation of glucose homeostasis. Nat Rev Neurosci 14(1):24–37

    Article  CAS  PubMed  Google Scholar 

  29. Cui H, Lopez M, Rahmouni K (2017) The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat Rev Endocrinol 13(6):338–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Koch M, Horvath TL (2014) Molecular and cellular regulation of hypothalamic melanocortin neurons controlling food intake and energy metabolism. Mol Psychiatry 19(7):752–761

    Article  CAS  PubMed  Google Scholar 

  31. Lavoie O, Michael NJ, Caron A (2023) A critical update on the leptin-melanocortin system. J Neurochem 165(4):467–486

    Article  CAS  PubMed  Google Scholar 

  32. Munzberg H, Bjornholm M, Bates SH, Myers MG Jr (2005) Leptin receptor action and mechanisms of leptin resistance. Cell Mol Life Sci 62(6):642–652

    Article  CAS  PubMed  Google Scholar 

  33. Skorupskaite K, George JT, Anderson RA (2014) The kisspeptin-GnRH pathway in human reproductive health and disease. Hum Reprod Update 20(4):485–500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tena-Sempere M (2017) Neuroendocrinology in 2016: neuroendocrine control of metabolism and reproduction. Nat Rev Endocrinol 13(2):67–68

    Article  CAS  PubMed  Google Scholar 

  35. Clarkson J, Herbison AE (2006) Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology 147(12):5817–5825

    Article  CAS  PubMed  Google Scholar 

  36. Yip SH, Boehm U, Herbison AE, Campbell RE (2015) Conditional viral tract tracing delineates the projections of the distinct kisspeptin neuron populations to gonadotropin-releasing hormone (GnRH) neurons in the mouse. Endocrinology 156(7):2582–2594

    Article  CAS  PubMed  Google Scholar 

  37. Irwig MS, Fraley GS, Smith JT, Acohido BV, Popa SM, Cunningham MJ, Gottsch ML, Clifton DK, Steiner RA (2004) Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology 80(4):264–272

    Article  CAS  PubMed  Google Scholar 

  38. Novaira HJ, Sonko ML, Hoffman G, Koo Y, Ko C, Wolfe A, Radovick S (2014) Disrupted kisspeptin signaling in GnRH neurons leads to hypogonadotrophic hypogonadism. Mol Endocrinol 28(2):225–238

    Article  PubMed  Google Scholar 

  39. Oakley AE, Clifton DK, Steiner RA (2009) Kisspeptin signaling in the brain. Endocr Rev 30(6):713–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Aguilera G, Liu Y (2012) The molecular physiology of CRH neurons. Front Neuroendocrinol 33(1):67–84

    Article  CAS  PubMed  Google Scholar 

  41. de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6(6):463–475

    Article  PubMed  Google Scholar 

  42. Zhou X, Lu Y, Zhao F, Dong J, Ma W, Zhong S, Wang M, Wang B, Zhao Y, Shi Y et al (2022) Deciphering the spatial-temporal transcriptional landscape of human hypothalamus development. Cell Stem Cell 29(2):328–343

    Article  CAS  PubMed  Google Scholar 

  43. Fenselau H, Campbell JN, Verstegen AM, Madara JC, Xu J, Shah BP, Resch JM, Yang Z, Mandelblat-Cerf Y, Livneh Y, Lowell BB (2017) A rapidly acting glutamatergic ARC–>PVH satiety circuit postsynaptically regulated by alpha-MSH. Nat Neurosci 20(1):42–51

    Article  CAS  PubMed  Google Scholar 

  44. Saucisse N, Mazier W, Simon V, Binder E, Catania C, Bellocchio L, Romanov RA, Leon S, Matias I, Zizzari P et al (2021) Functional heterogeneity of POMC neurons relies on mTORC1 signaling. Cell Rep 37(2):109800

    Article  CAS  PubMed  Google Scholar 

  45. Dicken MS, Tooker RE, Hentges ST (2012) Regulation of GABA and glutamate release from proopiomelanocortin neuron terminals in intact hypothalamic networks. J Neurosci 32(12):4042–4048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hentges ST, Nishiyama M, Overstreet LS, Stenzel-Poore M, Williams JT, Low MJ (2004) GABA release from proopiomelanocortin neurons. J Neurosci 24(7):1578–1583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hentges ST, Otero-Corchon V, Pennock RL, King CM, Low MJ (2009) Proopiomelanocortin expression in both GABA and glutamate neurons. J Neurosci 29(43):13684–13690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jarvie BC, Hentges ST (2012) Expression of GABAergic and glutamatergic phenotypic markers in hypothalamic proopiomelanocortin neurons. J Comp Neurol 520(17):3863–3876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Leon S, Simon V, Lee TH, Steuernagel L, Clark S, Biglari N, Leste-Lasserre T, Dupuy N, Cannich A, Bellocchio L et al (2024) Single cell tracing of Pomc neurons reveals recruitment of “Ghost” subtypes with atypical identity in a mouse model of obesity. Nat Commun 15(1):3443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Trotta M, Bello EP, Alsina R, Tavella MB, Ferran JL, Rubinstein M, Bumaschny VF (2020) Hypothalamic Pomc expression restricted to GABAergic neurons suppresses Npy overexpression and restores food intake in obese mice. Mol Metab 37:100985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18(23):9996–10015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Inutsuka A, Yamanaka A (2013) The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions. Front Endocrinol (Lausanne) 4:18

    Article  PubMed  Google Scholar 

  53. Li Y, Gao XB, Sakurai T, van den Pol AN (2002) Hypocretin/Orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system. Neuron 36(6):1169–1181

    Article  CAS  PubMed  Google Scholar 

  54. Schone C, Apergis-Schoute J, Sakurai T, Adamantidis A, Burdakov D (2014) Coreleased orexin and glutamate evoke nonredundant spike outputs and computations in histamine neurons. Cell Rep 7(3):697–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Eyigor O, Minbay Z, Kafa IM (2012) Glutamate and orexin neurons. Vitam Horm 89:209–222

    Article  CAS  PubMed  Google Scholar 

  56. Bubser M, Fadel JR, Jackson LL, Meador-Woodruff JH, Jing D, Deutch AY (2005) Dopaminergic regulation of orexin neurons. Eur J Neurosci 21(11):2993–3001

    Article  PubMed  Google Scholar 

  57. Saito YC, Tsujino N, Abe M, Yamazaki M, Sakimura K, Sakurai T (2018) Serotonergic input to orexin neurons plays a role in maintaining wakefulness and REM sleep architecture. Front Neurosci 12:892

    Article  PubMed  PubMed Central  Google Scholar 

  58. Ohno K, Hondo M, Sakurai T (2008) Cholinergic regulation of orexin/hypocretin neurons through M(3) muscarinic receptor in mice. J Pharmacol Sci 106(3):485–491

    Article  CAS  PubMed  Google Scholar 

  59. Williams KW, Margatho LO, Lee CE, Choi M, Lee S, Scott MM, Elias CF, Elmquist JK (2010) Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J Neurosci 30(7):2472–2479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sohn JW, Williams KW (2012) Functional heterogeneity of arcuate nucleus pro-opiomelanocortin neurons: implications for diverging melanocortin pathways. Mol Neurobiol 45(2):225–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Biglari N, Gaziano I, Schumacher J, Radermacher J, Paeger L, Klemm P, Chen W, Corneliussen S, Wunderlich CM, Sue M et al (2021) Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting. Nat Neurosci 24(7):913–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tucker JAL, Bornath DPD, McCarthy SF, Hazell TJ (2024) Leptin and energy balance: exploring Leptin’s role in the regulation of energy intake and energy expenditure. Nutr Neurosci 27(1):87–95

    Article  PubMed  Google Scholar 

  63. van Bloemendaal L, Ten Kulve JS, la Fleur SE, Ijzerman RG, Diamant M (2014) Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J Endocrinol 221(1):T1-16

    Article  PubMed  Google Scholar 

  64. Allard C, Cota D, Quarta C (2023) Poly-agonist pharmacotherapies for metabolic diseases: hopes and new challenges. Drugs. https://doi.org/10.1007/s40265-023-01982-6

    Article  PubMed  Google Scholar 

  65. Hill JW, Williams KW, Ye C, Luo J, Balthasar N, Coppari R, Cowley MA, Cantley LC, Lowell BB, Elmquist JK (2008) Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J Clin Invest 118(5):1796–1805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Dodd GT, Michael NJ, Lee-Young RS, Mangiafico SP, Pryor JT, Munder AC, Simonds SE, Bruning JC, Zhang ZY, Cowley MA et al (2018) Insulin regulates POMC neuronal plasticity to control glucose metabolism. Elife. https://doi.org/10.7554/eLife.38704

    Article  PubMed  PubMed Central  Google Scholar 

  67. Swanson LW, Kuypers HG (1980) A direct projection from the ventromedial nucleus and retrochiasmatic area of the hypothalamus to the medulla and spinal cord of the rat. Neurosci Lett 17(3):307–312

    Article  CAS  PubMed  Google Scholar 

  68. Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, Kuhar MJ, Saper CB, Elmquist JK (1998) Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 21(6):1375–1385

    Article  CAS  PubMed  Google Scholar 

  69. Horvath TL, Naftolin F, Kalra SP, Leranth C (1992) Neuropeptide-Y innervation of beta-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis. Endocrinology 131(5):2461–2467

    Article  CAS  PubMed  Google Scholar 

  70. Baker RA, Herkenham M (1995) Arcuate nucleus neurons that project to the hypothalamic paraventricular nucleus: neuropeptidergic identity and consequences of adrenalectomy on mRNA levels in the rat. J Comp Neurol 358(4):518–530

    Article  CAS  PubMed  Google Scholar 

  71. Le Tissier P, Campos P, Lafont C, Romano N, Hodson DJ, Mollard P (2017) An updated view of hypothalamic-vascular-pituitary unit function and plasticity. Nat Rev Endocrinol 13(5):257–267

    Article  PubMed  Google Scholar 

  72. Gao Y, Tschop MH, Luquet S (2014) Hypothalamic tanycytes: gatekeepers to metabolic control. Cell Metab 19(2):173–175

    Article  CAS  PubMed  Google Scholar 

  73. Prevot V, Dehouck B, Sharif A, Ciofi P, Giacobini P, Clasadonte J (2018) The versatile tanycyte: a hypothalamic integrator of reproduction and energy metabolism. Endocr Rev 39(3):333–368

    Article  PubMed  Google Scholar 

  74. Theodosis DT, Pierre K, Cadoret MA, Allard M, Faissner A, Poulain DA (1997) Expression of high levels of the extracellular matrix glycoprotein, tenascin-C, in the normal adult hypothalamoneurohypophysial system. J Comp Neurol 379(3):386–398

    Article  CAS  PubMed  Google Scholar 

  75. Horii-Hayashi N, Sasagawa T, Nishi M (2017) Insights from extracellular matrix studies in the hypothalamus: structural variations of perineuronal nets and discovering a new perifornical area of the anterior hypothalamus. Anat Sci Int 92(1):18–24

    Article  PubMed  Google Scholar 

  76. Vargova L, Sykova E (2014) Astrocytes and extracellular matrix in extrasynaptic volume transmission. Philos Trans R Soc Lond B Biol Sci 369(1654):20130608

    Article  PubMed  PubMed Central  Google Scholar 

  77. Akhmanova M, Osidak E, Domogatsky S, Rodin S, Domogatskaya A (2015) Physical, spatial, and molecular aspects of extracellular matrix of in vivo niches and artificial scaffolds relevant to stem cells research. Stem Cells Int 2015:167025

    Article  PubMed  PubMed Central  Google Scholar 

  78. Mirzadeh Z, Alonge KM, Cabrales E, Herranz-Perez V, Scarlett JM, Brown JM, Hassouna R, Matsen ME, Nguyen HT, Garcia-Verdugo JM et al (2019) Perineuronal net formation during the critical period for neuronal maturation in the hypothalamic arcuate nucleus. Nat Metab 1(2):212–221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Huang H, Joffrin AM, Zhao Y, Miller GM, Zhang GC, Oka Y, Hsieh-Wilson LC (2023) Chondroitin 4-O-sulfation regulates hippocampal perineuronal nets and social memory. Proc Natl Acad Sci U S A 120(24):e2301312120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Iwakura Y, Kobayashi Y, Namba H, Nawa H, Takei N (2024) Epidermal growth factor suppresses the development of gabaergic neurons via the modulation of perineuronal net formation in the neocortex of developing rodent brains. Neurochem Res 49(5):1347–1358

    Article  CAS  PubMed  Google Scholar 

  81. Sun J, Wang X, Sun R, Xiao X, Wang Y, Peng Y, Gao Y (2023) Microglia shape AgRP neuron postnatal development via regulating perineuronal net plasticity. Mol Psychiatry. https://doi.org/10.1038/s41380-023-02326-2

    Article  PubMed  PubMed Central  Google Scholar 

  82. Willis A, Pratt JA, Morris BJ (2022) Enzymatic degradation of cortical perineuronal nets reverses GABAergic interneuron maturation. Mol Neurobiol 59(5):2874–2893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chen S, Xu H, Dong S, Xiao L (2022) Morpho-electric properties and diversity of oxytocin neurons in paraventricular nucleus of hypothalamus in female and male mice. J Neurosci 42(14):2885–2904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Walter MH, Abele H, Plappert CF (2021) The role of oxytocin and the effect of stress during childbirth: neurobiological basics and implications for mother and child. Front Endocrinol (Lausanne) 12:742236

    Article  PubMed  Google Scholar 

  85. Dabrowska J, Hazra R, Ahern TH, Guo JD, McDonald AJ, Mascagni F, Muller JF, Young LJ, Rainnie DG (2011) Neuroanatomical evidence for reciprocal regulation of the corticotrophin-releasing factor and oxytocin systems in the hypothalamus and the bed nucleus of the stria terminalis of the rat: Implications for balancing stress and affect. Psychoneuroendocrinology 36(9):1312–1326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Eliava M, Melchior M, Knobloch-Bollmann HS, Wahis J, da Silva GM, Tang Y, Ciobanu AC, Triana Del Rio R, Roth LC, Althammer F et al (2016) A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing. Neuron 89(6):1291–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. McCarthy MM (2010) How it’s made: organisational effects of hormones on the developing brain. J Neuroendocrinol 22(7):736–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Tsukamura H, Homma T, Tomikawa J, Uenoyama Y, Maeda K (2010) Sexual differentiation of kisspeptin neurons responsible for sex difference in gonadotropin release in rats. Ann N Y Acad Sci 1200:95–103

    Article  CAS  PubMed  Google Scholar 

  89. Kauffman AS, Gottsch ML, Roa J, Byquist AC, Crown A, Clifton DK, Hoffman GE, Steiner RA, Tena-Sempere M (2007) Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology 148(4):1774–1783

    Article  CAS  PubMed  Google Scholar 

  90. Simerly RB (2002) Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci 25:507–536

    Article  CAS  PubMed  Google Scholar 

  91. Morris JA, Jordan CL, Breedlove SM (2004) Sexual differentiation of the vertebrate nervous system. Nat Neurosci 7(10):1034–1039

    Article  CAS  PubMed  Google Scholar 

  92. Homma T, Sakakibara M, Yamada S, Kinoshita M, Iwata K, Tomikawa J, Kanazawa T, Matsui H, Takatsu Y, Ohtaki T et al (2009) Significance of neonatal testicular sex steroids to defeminize anteroventral periventricular kisspeptin neurons and the GnRH/LH surge system in male rats. Biol Reprod 81(6):1216–1225

    Article  CAS  PubMed  Google Scholar 

  93. Clarkson J, Herbison AE (2016) Hypothalamic control of the male neonatal testosterone surge. Philos Trans R Soc Lond B Biol Sci 371(1688):20150115

    Article  PubMed  PubMed Central  Google Scholar 

  94. Wright CL, Schwarz JS, Dean SL, McCarthy MM (2010) Cellular mechanisms of estradiol-mediated sexual differentiation of the brain. Trends Endocrinol Metab 21(9):553–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bateman HL, Patisaul HB (2008) Disrupted female reproductive physiology following neonatal exposure to phytoestrogens or estrogen specific ligands is associated with decreased GnRH activation and kisspeptin fiber density in the hypothalamus. Neurotoxicology 29(6):988–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Clarkson J, Boon WC, Simpson ER, Herbison AE (2009) Postnatal development of an estradiol-kisspeptin positive feedback mechanism implicated in puberty onset. Endocrinology 150(7):3214–3220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Semaan SJ, Murray EK, Poling MC, Dhamija S, Forger NG, Kauffman AS (2010) BAX-dependent and BAX-independent regulation of Kiss1 neuron development in mice. Endocrinology 151(12):5807–5817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Mayer C, Acosta-Martinez M, Dubois SL, Wolfe A, Radovick S, Boehm U, Levine JE (2010) Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons. Proc Natl Acad Sci U S A 107(52):22693–22698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. van Veen JE, Kammel LG, Bunda PC, Shum M, Reid MS, Massa MG, Arneson D, Park JW, Zhang Z, Joseph AM et al (2020) Hypothalamic estrogen receptor alpha establishes a sexually dimorphic regulatory node of energy expenditure. Nat Metab 2(4):351–363

    Article  PubMed  PubMed Central  Google Scholar 

  100. Krause WC, Rodriguez R, Gegenhuber B, Matharu N, Rodriguez AN, Padilla-Roger AM, Toma K, Herber CB, Correa SM, Duan X et al (2021) Oestrogen engages brain MC4R signalling to drive physical activity in female mice. Nature 599(7883):131–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Correa SM, Newstrom DW, Warne JP, Flandin P, Cheung CC, Lin-Moore AT, Pierce AA, Xu AW, Rubenstein JL, Ingraham HA (2015) An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females. Cell Rep 10(1):62–74

    Article  CAS  PubMed  Google Scholar 

  102. Feng C, Wang Y, Zha X, Cao H, Huang S, Cao D, Zhang K, Xie T, Xu X, Liang Z, Zhang Z (2022) Cold-sensitive ventromedial hypothalamic neurons control homeostatic thermogenesis and social interaction-associated hyperthermia. Cell Metab 34(6):888–901

    Article  CAS  PubMed  Google Scholar 

  103. Shi H, Seeley RJ, Clegg DJ (2009) Sexual differences in the control of energy homeostasis. Front Neuroendocrinol 30(3):396–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Tramunt B, Smati S, Grandgeorge N, Lenfant F, Arnal JF, Montagner A, Gourdy P (2020) Sex differences in metabolic regulation and diabetes susceptibility. Diabetologia 63(3):453–461

    Article  PubMed  Google Scholar 

  105. Bermingham KM, Linenberg I, Hall WL, Kade K, Franks PW, Davies R, Wolf J, Hadjigeorgiou G, Asnicar F, Segata N et al (2022) Menopause is associated with postprandial metabolism, metabolic health and lifestyle: The ZOE PREDICT study. EBioMedicine 85:104303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Marlatt KL, Pitynski-Miller DR, Gavin KM, Moreau KL, Melanson EL, Santoro N, Kohrt WM (2022) Body composition and cardiometabolic health across the menopause transition. Obesity (Silver Spring) 30(1):14–27

    Article  PubMed  Google Scholar 

  107. Boldarine VT, Pedroso AP, Brandao-Teles C, LoTurco EG, Nascimento CMO, Oyama LM, Bueno AA, Martins-de-Souza D, Ribeiro EB (2020) Ovariectomy modifies lipid metabolism of retroperitoneal white fat in rats: a proteomic approach. Am J Physiol Endocrinol Metab 319(2):E427–E437

    Article  CAS  PubMed  Google Scholar 

  108. Costa-Beber LC, Goettems-Fiorin PB, Dos Santos JB, Friske PT, Frizzo MN, Heck TG, Hirsch GE, Ludwig MS (2021) Ovariectomy enhances female rats’ susceptibility to metabolic, oxidative, and heat shock response effects induced by a high-fat diet and fine particulate matter. Exp Gerontol 145:111215

    Article  CAS  PubMed  Google Scholar 

  109. Wang C, He Y, Xu P, Yang Y, Saito K, Xia Y, Yan X, Hinton A Jr, Yan C, Ding H et al (2018) TAp63 contributes to sexual dimorphism in POMC neuron functions and energy homeostasis. Nat Commun 9(1):1544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Burke LK, Doslikova B, D’Agostino G, Greenwald-Yarnell M, Georgescu T, Chianese R, Martinez de Morentin PB, Ogunnowo-Bada E, Cansell C, Valencia-Torres L et al (2016) Sex difference in physical activity, energy expenditure and obesity driven by a subpopulation of hypothalamic POMC neurons. Mol Metab 5(3):245–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Gonzalez-Garcia I, Garcia-Clave E, Cebrian-Serrano A, Le Thuc O, Contreras RE, Xu Y, Gruber T, Schriever SC, Legutko B, Lintelmann J et al (2023) Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1. Cell Metab 35(3):438–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Xu AW, Ste-Marie L, Kaelin CB, Barsh GS (2007) Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology 148(1):72–80

    Article  CAS  PubMed  Google Scholar 

  113. Xu Y, Nedungadi TP, Zhu L, Sobhani N, Irani BG, Davis KE, Zhang X, Zou F, Gent LM, Hahner LD et al (2011) Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab 14(4):453–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Yang Y, van der Klaauw AA, Zhu L, Cacciottolo TM, He Y, Stadler LKJ, Wang C, Xu P, Saito K, Hinton A Jr et al (2019) Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis. Nat Commun 10(1):1718

    Article  PubMed  PubMed Central  Google Scholar 

  115. Yu M, Bean JC, Liu H, He Y, Yang Y, Cai X, Yu K, Pei Z, Liu H, Tu L et al (2022) SK3 in POMC neurons plays a sexually dimorphic role in energy and glucose homeostasis. Cell Biosci 12(1):170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Mansano NDS, Vieira HR, Araujo-Lopes R, Szawka RE, Donato J Jr, Frazao R (2023) Fasting modulates GABAergic synaptic transmission to arcuate kisspeptin neurons in female mice. Endocrinology. https://doi.org/10.1210/endocr/bqad150

    Article  PubMed  Google Scholar 

  117. Han Y, He Y, Harris L, Xu Y, Wu Q (2023) Identification of a GABAergic neural circuit governing leptin signaling deficiency-induced obesity. Elife. https://doi.org/10.7554/eLife.8264

    Article  PubMed  PubMed Central  Google Scholar 

  118. Egan OK, Inglis MA, Anderson GM (2017) Leptin signaling in AgRP neurons modulates puberty onset and adult fertility in mice. J Neurosci 37(14):3875–3886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Padilla SL, Qiu J, Nestor CC, Zhang C, Smith AW, Whiddon BB, Ronnekleiv OK, Kelly MJ, Palmiter RD (2017) AgRP to kiss1 neuron signaling links nutritional state and fertility. Proc Natl Acad Sci U S A 114(9):2413–2418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Decourt C, Connolly G, Ancel C, Inglis MA, Anderson GM (2022) Agouti-related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice. J Neuroendocrinol 34(10):e13190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Wang L, Moenter SM (2020) Differential roles of hypothalamic AVPV and arcuate kisspeptin neurons in estradiol feedback regulation of female reproduction. Neuroendocrinology 110(3–4):172–184

    Article  CAS  PubMed  Google Scholar 

  122. Fu LY, van den Pol AN (2010) Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J Neurosci 30(30):10205–10219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Qiu J, Rivera HM, Bosch MA, Padilla SL, Stincic TL, Palmiter RD, Kelly MJ, Ronnekleiv OK (2018) Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females. Elife. https://doi.org/10.7554/eLife.35656

    Article  PubMed  PubMed Central  Google Scholar 

  124. Narita K, Nagao K, Bannai M, Ichimaru T, Nakano S, Murata T, Higuchi T, Takahashi M (2011) Dietary deficiency of essential amino acids rapidly induces cessation of the rat estrous cycle. PLoS ONE 6(11):e28136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Alonso-Caraballo Y, Ferrario CR (2019) Effects of the estrous cycle and ovarian hormones on cue-triggered motivation and intrinsic excitability of medium spiny neurons in the nucleus accumbens core of female rats. Horm Behav 116:104583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Schneider JE, Wise JD, Benton NA, Brozek JM, Keen-Rhinehart E (2013) When do we eat? Ingestive behavior, survival, and reproductive success. Horm Behav 64(4):702–728

    Article  CAS  PubMed  Google Scholar 

  127. Olofsson LE, Pierce AA, Xu AW (2009) Functional requirement of AgRP and NPY neurons in ovarian cycle-dependent regulation of food intake. Proc Natl Acad Sci U S A 106(37):15932–15937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Smith AW, Bosch MA, Wagner EJ, Ronnekleiv OK, Kelly MJ (2013) The membrane estrogen receptor ligand STX rapidly enhances GABAergic signaling in NPY/AgRP neurons: role in mediating the anorexigenic effects of 17beta-estradiol. Am J Physiol Endocrinol Metab 305(5):E632–E640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Xu AW, Kaelin CB, Morton GJ, Ogimoto K, Stanhope K, Graham J, Baskin DG, Havel P, Schwartz MW, Barsh GS (2005) Effects of hypothalamic neurodegeneration on energy balance. PLoS Biol 3(12):e415

    Article  PubMed  PubMed Central  Google Scholar 

  130. Takeo T, Chiba Y, Sakuma Y (1993) Suppression of the lordosis reflex of female rats by efferents of the medial preoptic area. Physiol Behav 53(5):831–838

    Article  CAS  PubMed  Google Scholar 

  131. Eckersell CB, Popper P, Micevych PE (1998) Estrogen-induced alteration of mu-opioid receptor immunoreactivity in the medial preoptic nucleus and medial amygdala. J Neurosci 18(10):3967–3976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Sinchak K, Micevych PE (2001) Progesterone blockade of estrogen activation of mu-opioid receptors regulates reproductive behavior. J Neurosci 21(15):5723–5729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Mills RH, Sohn RK, Micevych PE (2004) Estrogen-induced mu-opioid receptor internalization in the medial preoptic nucleus is mediated via neuropeptide Y-Y1 receptor activation in the arcuate nucleus of female rats. J Neurosci 24(4):947–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Dewing P, Boulware MI, Sinchak K, Christensen A, Mermelstein PG, Micevych P (2007) Membrane estrogen receptor-alpha interactions with metabotropic glutamate receptor 1a modulate female sexual receptivity in rats. J Neurosci 27(35):9294–9300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Sanathara NM, Moreas J, Mahavongtrakul M, Sinchak K (2014) Estradiol upregulates progesterone receptor and orphanin FQ colocalization in arcuate nucleus neurons and opioid receptor-like receptor-1 expression in proopiomelanocortin neurons that project to the medial preoptic nucleus in the female rat. Neuroendocrinology 100(2–3):103–118

    Article  CAS  PubMed  Google Scholar 

  136. Yin L, Hashikawa K, Hashikawa Y, Osakada T, Lischinsky JE, Diaz V, Lin D (2022) VMHvll(Cckar) cells dynamically control female sexual behaviors over the reproductive cycle. Neuron 110(18):3000–3017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Martinez de Morentin PB, Gonzalez-Garcia I, Martins L, Lage R, Fernandez-Mallo D, Martinez-Sanchez N, Ruiz-Pino F, Liu J, Morgan DA, Pinilla L et al (2014) Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metab 20(1):41–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Ye H, Feng B, Wang C, Saito K, Yang Y, Ibrahimi L, Schaul S, Patel N, Saenz L, Luo P et al (2022) An estrogen-sensitive hypothalamus-midbrain neural circuit controls thermogenesis and physical activity. Sci Adv 8(3):0185

    Article  Google Scholar 

  139. Douglass AM, Resch JM, Madara JC, Kucukdereli H, Yizhar O, Grama A, Yamagata M, Yang Z, Lowell BB (2023) Neural basis for fasting activation of the hypothalamic-pituitary-adrenal axis. Nature 620(7972):154–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Zhang Y, Du C, Wang W, Qiao W, Li Y, Zhang Y, Sheng S, Zhou X, Zhang L, Fan H et al (2024) Glucocorticoids increase adiposity by stimulating Kruppel-like factor 9 expression in macrophages. Nat Commun 15(1):1190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Fernandez G, Cabral A, De Francesco PN, Uriarte M, Reynaldo M, Castrogiovanni D, Zubiria G, Giovambattista A, Cantel S, Denoyelle S et al (2022) GHSR controls food deprivation-induced activation of CRF neurons of the hypothalamic paraventricular nucleus in a LEAP2-dependent manner. Cell Mol Life Sci 79(5):277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Yuan Y, Wu W, Chen M, Cai F, Fan C, Shen W, Sun W, Hu J (2019) Reward inhibits paraventricular CRH neurons to relieve stress. Curr Biol 29(7):1243–1251

    Article  CAS  PubMed  Google Scholar 

  143. Kim J, Lee S, Fang YY, Shin A, Park S, Hashikawa K, Bhat S, Kim D, Sohn JW, Lin D, Suh GSB (2019) Rapid, biphasic CRF neuronal responses encode positive and negative valence. Nat Neurosci 22(4):576–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. de Kloet ER, Karst H, Joels M (2008) Corticosteroid hormones in the central stress response: quick-and-slow. Front Neuroendocrinol 29(2):268–272

    Article  PubMed  Google Scholar 

  145. Jiang Z, Chen C, Weiss GL, Fu X, Stelly CE, Sweeten BLW, Tirrell PS, Pursell I, Stevens CR, Fisher MO et al (2022) Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice. Cell Rep 41(3):111509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Evanson NK, Tasker JG, Hill MN, Hillard CJ, Herman JP (2010) Fast feedback inhibition of the HPA axis by glucocorticoids is mediated by endocannabinoid signaling. Endocrinology 151(10):4811–4819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Ga R, Campbell EJ, Walker LC, S SCn, Muthmainah M, F SK, A MG, O’Shea MJ, He S, Dayas CV, et al (2023) A paraventricular thalamus to insular cortex glutamatergic projection gates “emotional” stress-induced binge eating in females. Neuropsychopharmacology 48(13):1931–1940

    Article  Google Scholar 

  148. Fischer S, Breithaupt L, Wonderlich J, Westwater ML, Crosby RD, Engel SG, Thompson J, Lavender J, Wonderlich S (2017) Impact of the neural correlates of stress and cue reactivity on stress related binge eating in the natural environment. J Psychiatr Res 92:15–23

    Article  PubMed  Google Scholar 

  149. Lim MC, Parsons S, Goglio A, Fox E (2021) Anxiety, stress, and binge eating tendencies in adolescence: a prospective approach. J Eat Disord 9(1):94

    Article  PubMed  PubMed Central  Google Scholar 

  150. Luby JL, Baram TZ, Rogers CE, Barch DM (2020) Neurodevelopmental optimization after early-life adversity: cross-species studies to elucidate sensitive periods and brain mechanisms to inform early intervention. Trends Neurosci 43(10):744–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Gee DG (2021) Early adversity and development: parsing heterogeneity and identifying pathways of risk and resilience. Am J Psychiatry 178(11):998–1013

    Article  PubMed  Google Scholar 

  152. Molet J, Heins K, Zhuo X, Mei YT, Regev L, Baram TZ, Stern H (2016) Fragmentation and high entropy of neonatal experience predict adolescent emotional outcome. Transl Psychiatry 6(1):e702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Bolton JL, Molet J, Regev L, Chen Y, Rismanchi N, Haddad E, Yang DZ, Obenaus A, Baram TZ (2018) Anhedonia following early-life adversity involves aberrant interaction of reward and anxiety circuits and is reversed by partial silencing of amygdala corticotropin-releasing hormone gene. Biol Psychiatry 83(2):137–147

    Article  CAS  PubMed  Google Scholar 

  154. Levis SC, Bentzley BS, Molet J, Bolton JL, Perrone CR, Baram TZ, Mahler SV (2021) On the early life origins of vulnerability to opioid addiction. Mol Psychiatry 26(8):4409–4416

    Article  PubMed  Google Scholar 

  155. Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35(3):537–555

    Article  PubMed  Google Scholar 

  156. Gunn BG, Cunningham L, Cooper MA, Corteen NL, Seifi M, Swinny JD, Lambert JJ, Belelli D (2013) Dysfunctional astrocytic and synaptic regulation of hypothalamic glutamatergic transmission in a mouse model of early-life adversity: relevance to neurosteroids and programming of the stress response. J Neurosci 33(50):19534–19554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Bolton JL, Short AK, Othy S, Kooiker CL, Shao M, Gunn BG, Beck J, Bai X, Law SM, Savage JC et al (2022) Early stress-induced impaired microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses. Cell Rep 38(13):110600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Short AK, Thai CW, Chen Y, Kamei N, Pham AL, Birnie MT, Bolton JL, Mortazavi A, Baram TZ (2023) Single-cell transcriptional changes in hypothalamic corticotropin-releasing factor-expressing neurons after early-life adversity inform enduring alterations in vulnerabilities to stress. Biol Psychiatry Glob Open Sci 3(1):99–109

    Article  PubMed  Google Scholar 

  159. Korosi A, Shanabrough M, McClelland S, Liu ZW, Borok E, Gao XB, Horvath TL, Baram TZ (2010) Early-life experience reduces excitation to stress-responsive hypothalamic neurons and reprograms the expression of corticotropin-releasing hormone. J Neurosci 30(2):703–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Singh-Taylor A, Molet J, Jiang S, Korosi A, Bolton JL, Noam Y, Simeone K, Cope J, Chen Y, Mortazavi A, Baram TZ (2018) NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience. Mol Psychiatry 23(3):648–657

    Article  CAS  PubMed  Google Scholar 

  161. Fenoglio KA, Brunson KL, Avishai-Eliner S, Chen Y, Baram TZ (2004) Region-specific onset of handling-induced changes in corticotropin-releasing factor and glucocorticoid receptor expression. Endocrinology 145(6):2702–2706

    Article  CAS  PubMed  Google Scholar 

  162. Plotsky PM, Thrivikraman KV, Nemeroff CB, Caldji C, Sharma S, Meaney MJ (2005) Long-term consequences of neonatal rearing on central corticotropin-releasing factor systems in adult male rat offspring. Neuropsychopharmacology 30(12):2192–2204

    Article  CAS  PubMed  Google Scholar 

  163. Shin S, You IJ, Jeong M, Bae Y, Wang XY, Cawley ML, Han A, Lim BK (2023) Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus-brainstem pathway. Nat Neurosci 26(1):79–91

    Article  CAS  PubMed  Google Scholar 

  164. Attig L, Solomon G, Ferezou J, Abdennebi-Najar L, Taouis M, Gertler A, Djiane J (2008) Early postnatal leptin blockage leads to a long-term leptin resistance and susceptibility to diet-induced obesity in rats. Int J Obes (Lond) 32(7):1153–1160

    Article  CAS  PubMed  Google Scholar 

  165. McCormick CM, Kehoe P, Kovacs S (1998) Corticosterone release in response to repeated, short episodes of neonatal isolation: evidence of sensitization. Int J Dev Neurosci 16(3–4):175–185

    Article  CAS  PubMed  Google Scholar 

  166. Power EM, Iremonger KJ (2021) Plasticity of intrinsic excitability across the estrous cycle in hypothalamic CRH neurons. Sci Rep 11(1):16700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Li XF, Bowe JE, Lightman SL, O’Byrne KT (2005) Role of corticotropin-releasing factor receptor-2 in stress-induced suppression of pulsatile luteinizing hormone secretion in the rat. Endocrinology 146(1):318–322

    Article  CAS  PubMed  Google Scholar 

  168. Li XF, Bowe JE, Kinsey-Jones JS, Brain SD, Lightman SL, O’Byrne KT (2006) Differential role of corticotrophin-releasing factor receptor types 1 and 2 in stress-induced suppression of pulsatile luteinising hormone secretion in the female rat. J Neuroendocrinol 18(8):602–610

    Article  CAS  PubMed  Google Scholar 

  169. Cagampang FR, Cates PS, Sandhu S, Strutton PH, McGarvey C, Coen CW, O’Byrne KT (1997) Hypoglycaemia-induced inhibition of pulsatile luteinizing hormone secretion in female rats: role of oestradiol, endogenous opioids and the adrenal medulla. J Neuroendocrinol 9(11):867–872

    Article  CAS  PubMed  Google Scholar 

  170. Li XF, Mitchell JC, Wood S, Coen CW, Lightman SL, O’Byrne KT (2003) The effect of oestradiol and progesterone on hypoglycaemic stress-induced suppression of pulsatile luteinizing hormone release and on corticotropin-releasing hormone mRNA expression in the rat. J Neuroendocrinol 15(5):468–476

    Article  CAS  PubMed  Google Scholar 

  171. Cates PS, Li XF, O’Byrne KT (2004) The influence of 17beta-oestradiol on corticotrophin-releasing hormone induced suppression of luteinising hormone pulses and the role of CRH in hypoglycaemic stress-induced suppression of pulsatile LH secretion in the female rat. Stress 7(2):113–118

    Article  CAS  PubMed  Google Scholar 

  172. Wagenmaker ER, Moenter SM (2017) Exposure to acute psychosocial stress disrupts the luteinizing hormone surge independent of estrous cycle alterations in female mice. Endocrinology 158(8):2593–2602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Phumsatitpong C, Moenter SM (2018) Estradiol-dependent stimulation and suppression of gonadotropin-releasing hormone neuron firing activity by corticotropin-releasing hormone in female mice. Endocrinology 159(1):414–425

    Article  CAS  PubMed  Google Scholar 

  174. Sohn JW, Xu Y, Jones JE, Wickman K, Williams KW, Elmquist JK (2011) Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels. Neuron 71(3):488–497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Lam BYH, Cimino I, Polex-Wolf J, Nicole Kohnke S, Rimmington D, Iyemere V, Heeley N, Cossetti C, Schulte R, Saraiva LR et al (2017) Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing. Mol Metab 6(5):383–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Campbell JN, Macosko EZ, Fenselau H, Pers TH, Lyubetskaya A, Tenen D, Goldman M, Verstegen AM, Resch JM, McCarroll SA et al (2017) A molecular census of arcuate hypothalamus and median eminence cell types. Nat Neurosci 20(3):484–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Quarta C, Claret M, Zeltser LM, Williams KW, Yeo GSH, Tschop MH, Diano S, Bruning JC, Cota D (2021) POMC neuronal heterogeneity in energy balance and beyond: an integrated view. Nat Metab 3(3):299–308

    Article  PubMed  PubMed Central  Google Scholar 

  178. Betley JN, Xu S, Cao ZFH, Gong R, Magnus CJ, Yu Y, Sternson SM (2015) Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521(7551):180–185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Mandelblat-Cerf Y, Ramesh RN, Burgess CR, Patella P, Yang Z, Lowell BB, Andermann ML (2015) Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. Elife. https://doi.org/10.7554/eLife.07122

    Article  PubMed  PubMed Central  Google Scholar 

  180. Huisman C, Cho H, Brock O, Lim SJ, Youn SM, Park Y, Kim S, Lee SK, Delogu A, Lee JW (2019) Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators. Nat Commun 10(1):3696

    Article  PubMed  PubMed Central  Google Scholar 

  181. Chung D, Shum A, Caraveo G (2020) GAP-43 and BASP1 in axon regeneration: implications for the treatment of neurodegenerative diseases. Front Cell Dev Biol 8:567537

    Article  PubMed  PubMed Central  Google Scholar 

  182. Kuperman Y, Weiss M, Dine J, Staikin K, Golani O, Ramot A, Nahum T, Kuhne C, Shemesh Y, Wurst W et al (2016) CRFR1 in AgRP neurons modulates sympathetic nervous system activity to adapt to cold stress and fasting. Cell Metab 23(6):1185–1199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Chen W, Mehlkop O, Scharn A, Nolte H, Klemm P, Henschke S, Steuernagel L, Sotelo-Hitschfeld T, Kaya E, Wunderlich CM et al (2023) Nutrient-sensing AgRP neurons relay control of liver autophagy during energy deprivation. Cell Metab 35(5):786–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Palmiter RD (2007) Is dopamine a physiologically relevant mediator of feeding behavior? Trends Neurosci 30(8):375–381

    Article  CAS  PubMed  Google Scholar 

  185. Szczypka MS, Rainey MA, Kim DS, Alaynick WA, Marck BT, Matsumoto AM, Palmiter RD (1999) Feeding behavior in dopamine-deficient mice. Proc Natl Acad Sci U S A 96(21):12138–12143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Zhang Q, Tang Q, Purohit NM, Davenport JB, Brennan C, Patel RK, Godschall E, Zwiefel LS, Spano A, Campbell JN, Guler AD (2022) Food-induced dopamine signaling in AgRP neurons promotes feeding. Cell Rep 41(9):111718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Alhadeff AL, Goldstein N, Park O, Klima ML, Vargas A, Betley JN (2019) Natural and drug rewards engage distinct pathways that converge on coordinated hypothalamic and reward circuits. Neuron 103(5):891–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Mazzone CM, Liang-Guallpa J, Li C, Wolcott NS, Boone MH, Southern M, Kobzar NP, Salgado IA, Reddy DM, Sun F et al (2020) High-fat food biases hypothalamic and mesolimbic expression of consummatory drives. Nat Neurosci 23(10):1253–1266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Reichenbach A, Clarke RE, Stark R, Lockie SH, Mequinion M, Dempsey H, Rawlinson S, Reed F, Sepehrizadeh T, DeVeer M et al (2022) Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum. Elife. https://doi.org/10.7554/eLife.72668

    Article  PubMed  PubMed Central  Google Scholar 

  190. Kumar D, Candlish M, Periasamy V, Avcu N, Mayer C, Boehm U (2015) Specialized subpopulations of kisspeptin neurons communicate with GnRH neurons in female mice. Endocrinology 156(1):32–38

    Article  PubMed  Google Scholar 

  191. Matsuda F, Ohkura S, Magata F, Munetomo A, Chen J, Sato M, Inoue N, Uenoyama Y, Tsukamura H (2019) Role of kisspeptin neurons as a GnRH surge generator: comparative aspects in rodents and non-rodent mammals. J Obstet Gynaecol Res 45(12):2318–2329

    Article  CAS  PubMed  Google Scholar 

  192. Moore AM, Coolen LM, Lehman MN (2022) In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.2117767119

    Article  PubMed  PubMed Central  Google Scholar 

  193. Porteous R, Petersen SL, Yeo SH, Bhattarai JP, Ciofi P, de Tassigny XD, Colledge WH, Caraty A, Herbison AE (2011) Kisspeptin neurons co-express met-enkephalin and galanin in the rostral periventricular region of the female mouse hypothalamus. J Comp Neurol 519(17):3456–3469

    Article  CAS  PubMed  Google Scholar 

  194. Manchishi S, Prater M, Colledge WH (2024) Transcriptional profiling of Kiss1 neurons from arcuate and rostral periventricular hypothalamic regions in female mice. Reproduction. https://doi.org/10.1530/REP-23-0342

    Article  PubMed  Google Scholar 

  195. Cheng G, Coolen LM, Padmanabhan V, Goodman RL, Lehman MN (2010) The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology 151(1):301–311

    Article  CAS  PubMed  Google Scholar 

  196. Zhou S, Zang S, Hu Y, Shen Y, Li H, Chen W, Li P, Shen Y (2022) Transcriptome-scale spatial gene expression in rat arcuate nucleus during puberty. Cell Biosci 12(1):8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Clarkson J, Herbison AE (2011) Dual phenotype kisspeptin-dopamine neurones of the rostral periventricular area of the third ventricle project to gonadotrophin-releasing hormone neurones. J Neuroendocrinol 23(4):293–301

    Article  CAS  PubMed  Google Scholar 

  198. Stephens SBZ, Rouse ML, Tolson KP, Liaw RB, Parra RA, Chahal N, Kauffman AS (2017) Effects of Selective Deletion of Tyrosine Hydroxylase from Kisspeptin Cells on Puberty and Reproduction in Male and Female Mice. eNeuro. https://doi.org/10.1523/ENEURO.0150-17.201

    Article  PubMed  PubMed Central  Google Scholar 

  199. Krajewski SJ, Anderson MJ, Iles-Shih L, Chen KJ, Urbanski HF, Rance NE (2005) Morphologic evidence that neurokinin B modulates gonadotropin-releasing hormone secretion via neurokinin 3 receptors in the rat median eminence. J Comp Neurol 489(3):372–386

    Article  CAS  PubMed  Google Scholar 

  200. Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, Serin A, Mungan NO, Cook JR, Imamoglu S et al (2009) TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nat Genet 41(3):354–358

    Article  CAS  PubMed  Google Scholar 

  201. Uenoyama Y, Tsuchida H, Nagae M, Inoue N, Tsukamura H (2022) Opioidergic pathways and kisspeptin in the regulation of female reproduction in mammals. Front Neurosci 16:958377

    Article  PubMed  PubMed Central  Google Scholar 

  202. Nakamura S, Watanabe Y, Goto T, Ikegami K, Inoue N, Uenoyama Y, Tsukamura H (2022) Kisspeptin neurons as a key player bridging the endocrine system and sexual behavior in mammals. Front Neuroendocrinol 64:100952

    Article  CAS  PubMed  Google Scholar 

  203. Ramos-Pittol JM, Fernandes-Freitas I, Milona A, Manchishi SM, Rainbow K, Lam BYH, Tadross JA, Beucher A, Colledge WH, Cebola I et al (2023) Dax1 modulates ERalpha-dependent hypothalamic estrogen sensing in female mice. Nat Commun 14(1):3076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Smith JT (2013) Sex steroid regulation of kisspeptin circuits. Adv Exp Med Biol 784:275–295

    Article  CAS  PubMed  Google Scholar 

  205. Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner RA (2005) Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology 146(9):3686–3692

    Article  CAS  PubMed  Google Scholar 

  206. Gocz B, Takacs S, Skrapits K, Rumpler E, Solymosi N, Poliska S, Colledge WH, Hrabovszky E, Sarvari M (2022) Estrogen differentially regulates transcriptional landscapes of preoptic and arcuate kisspeptin neuron populations. Front Endocrinol (Lausanne) 13:960769

    Article  PubMed  Google Scholar 

  207. Campbell RE, Coolen LM, Hoffman GE, Hrabovszky E (2022) Highlights of neuroanatomical discoveries of the mammalian gonadotropin-releasing hormone system. J Neuroendocrinol 34(5):e13115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Shan Y, Saadi H, Wray S (2020) Heterogeneous origin of gonadotropin releasing hormone-1 neurons in mouse embryos detected by islet-1/2 expression. Front Cell Dev Biol 8:35

    Article  PubMed  PubMed Central  Google Scholar 

  209. Duittoz AH, Tillet Y, Geller S (2022) The great migration: How glial cells could regulate GnRH neuron development and shape adult reproductive life. J Chem Neuroanat 125:102149

    Article  CAS  PubMed  Google Scholar 

  210. Pellegrino G, Martin M, Allet C, Lhomme T, Geller S, Franssen D, Mansuy V, Manfredi-Lozano M, Coutteau-Robles A, Delli V et al (2021) GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation. Nat Neurosci 24(12):1660–1672

    Article  CAS  PubMed  Google Scholar 

  211. Cannarella R, Paganoni AJJ, Cicolari S, Oleari R, Condorelli RA, La Vignera S, Cariboni A, Calogero AE, Magni P (2021) Anti-mullerian hormone, growth hormone, and insulin-like growth factor 1 modulate the migratory and secretory patterns of GnRH neurons. Int J Mol Sci 22(5):2445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Paganoni AJJ, Cannarella R, Oleari R, Amoruso F, Antal R, Ruzza M, Olivieri C, Condorelli RA, La Vignera S, Tolaj F et al (2023) Insulin-like growth factor 1, growth hormone, and anti-mullerian hormone receptors are differentially expressed during gnrh neuron development. Int J Mol Sci 24(17):13073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Wierman ME, Kiseljak-Vassiliades K, Tobet S (2011) Gonadotropin-releasing hormone (GnRH) neuron migration: initiation, maintenance and cessation as critical steps to ensure normal reproductive function. Front Neuroendocrinol 32(1):43–52

    Article  CAS  PubMed  Google Scholar 

  214. Levine JE, Norman RL, Gliessman PM, Oyama TT, Bangsberg DR, Spies HG (1985) In vivo gonadotropin-releasing hormone release and serum luteinizing hormone measurements in ovariectomized, estrogen-treated rhesus macaques. Endocrinology 117(2):711–721

    Article  CAS  PubMed  Google Scholar 

  215. Moffitt JR, Bambah-Mukku D, Eichhorn SW, Vaughn E, Shekhar K, Perez JD, Rubinstein ND, Hao J, Regev A, Dulac C, Zhuang X (2018) Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region. Science. https://doi.org/10.1126/science.aau5324

    Article  PubMed  PubMed Central  Google Scholar 

  216. Bardoczi Z, Wilheim T, Skrapits K, Hrabovszky E, Racz G, Matolcsy A, Liposits Z, Sliwowska JH, Dobolyi A, Kallo I (2018) GnRH neurons provide direct input to hypothalamic tyrosine hydroxylase immunoreactive neurons which is maintained during lactation. Front Endocrinol (Lausanne) 9:685

    Article  PubMed  Google Scholar 

  217. Mitchell V, Loyens A, Spergel DJ, Flactif M, Poulain P, Tramu G, Beauvillain JC (2003) A confocal microscopic study of gonadotropin-releasing hormone (GnRH) neuron inputs to dopaminergic neurons containing estrogen receptor alpha in the arcuate nucleus of GnRH-green fluorescent protein transgenic mice. Neuroendocrinology 77(3):198–207

    Article  CAS  PubMed  Google Scholar 

  218. Romanov RA, Alpar A, Hokfelt T, Harkany T (2017) Molecular diversity of corticotropin-releasing hormone mRNA-containing neurons in the hypothalamus. J Endocrinol 232(3):R161–R172

    Article  CAS  PubMed  Google Scholar 

  219. Berkhout JB, Poormoghadam D, Yi C, Kalsbeek A, Meijer OC, Mahfouz A (2024) An integrated single-cell RNA-seq atlas of the mouse hypothalamic paraventricular nucleus links transcriptomic and functional types. J Neuroendocrinol 36(2):e13367

    Article  CAS  PubMed  Google Scholar 

  220. Jeanneteau FD, Lambert WM, Ismaili N, Bath KG, Lee FS, Garabedian MJ, Chao MV (2012) BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus. Proc Natl Acad Sci U S A 109(4):1305–1310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Gillies GE, Linton EA, Lowry PJ (1982) Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin. Nature 299(5881):355–357

    Article  CAS  PubMed  Google Scholar 

  222. Itoi K, Helmreich DL, Lopez-Figueroa MO, Watson SJ (1999) Differential regulation of corticotropin-releasing hormone and vasopressin gene transcription in the hypothalamus by norepinephrine. J Neurosci 19(13):5464–5472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Erkut ZA, Pool C, Swaab DF (1998) Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons. J Clin Endocrinol Metab 83(6):2066–2073

    CAS  PubMed  Google Scholar 

  224. Romanov RA, Alpar A, Zhang MD, Zeisel A, Calas A, Landry M, Fuszard M, Shirran SL, Schnell R, Dobolyi A et al (2015) A secretagogin locus of the mammalian hypothalamus controls stress hormone release. EMBO J 34(1):36–54

    Article  CAS  PubMed  Google Scholar 

  225. de Kloet AD, Wang L, Pitra S, Hiller H, Smith JA, Tan Y, Nguyen D, Cahill KM, Sumners C, Stern JE, Krause EG (2017) A unique, “angiotensin-sensitive” neuronal population coordinates neuroendocrine, cardiovascular, and behavioral responses to stress. J Neurosci 37(13):3478–3490

    Article  PubMed  PubMed Central  Google Scholar 

  226. Clasadonte J, Prevot V (2018) The special relationship: glia-neuron interactions in the neuroendocrine hypothalamus. Nat Rev Endocrinol 14(1):25–44

    Article  CAS  PubMed  Google Scholar 

  227. Kohnke S, Buller S, Nuzzaci D, Ridley K, Lam B, Pivonkova H, Bentsen MA, Alonge KM, Zhao C, Tadross J et al (2021) Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence. Cell Rep 36(2):109362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Garcia-Caceres C, Balland E, Prevot V, Luquet S, Woods SC, Koch M, Horvath TL, Yi CX, Chowen JA, Verkhratsky A et al (2019) Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nat Neurosci 22(1):7–14

    Article  CAS  PubMed  Google Scholar 

  229. Xu Y, Yang D, Wang L, Krol E, Mazidi M, Li L, Huang Y, Niu C, Liu X, Lam SM et al (2023) Maternal high fat diet in lactation impacts hypothalamic neurogenesis and neurotrophic development, leading to later life susceptibility to obesity in male but not female mice. Adv Sci (Weinh) 10(35):e2305472

    Article  PubMed  Google Scholar 

  230. Mainardi M, Scabia G, Vottari T, Santini F, Pinchera A, Maffei L, Pizzorusso T, Maffei M (2010) A sensitive period for environmental regulation of eating behavior and leptin sensitivity. Proc Natl Acad Sci U S A 107(38):16673–16678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Patterson CM, Dunn-Meynell AA, Levin BE (2008) Three weeks of early-onset exercise prolongs obesity resistance in DIO rats after exercise cessation. Am J Physiol Regul Integr Comp Physiol 294(2):R290-301

    Article  CAS  PubMed  Google Scholar 

  232. He Z, Gao Y, Alhadeff AL, Castorena CM, Huang Y, Lieu L, Afrin S, Sun J, Betley JN, Guo H, Williams KW (2018) Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise. Mol Metab 18:107–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Mainardi M, Pizzorusso T, Maffei M (2013) Environment, leptin sensitivity, and hypothalamic plasticity. Neural Plast 2013:438072

    Article  PubMed  PubMed Central  Google Scholar 

  234. Scabia G, Barone I, Mainardi M, Ceccarini G, Scali M, Buzzigoli E, Dattilo A, Vitti P, Gastaldelli A, Santini F et al (2018) The antidepressant fluoxetine acts on energy balance and leptin sensitivity via BDNF. Sci Rep 8(1):1781

    Article  PubMed  PubMed Central  Google Scholar 

  235. Barone I, Melani R, Mainardi M, Scabia G, Scali M, Dattilo A, Ceccarini G, Vitti P, Santini F, Maffei L et al (2018) Fluoxetine Modulates the Activity of Hypothalamic POMC Neurons via mTOR Signaling. Mol Neurobiol 55(12):9267–9279

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

CQ acknowledges INSERM, the European Research Council (ERCcog project 101124230 — Ghostbuster), the University of Bordeaux, Agencie Nationale Recherche (ANR-20-CE14-0046), French Societies of Endocrinology, Nutrition, and Diabetes (SFE, SFN, and SFD), Fyssen Foundation, and Institut Benjamin Delessert.

Author information

Authors and Affiliations

  1. University of Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000, Bordeaux, France

    T. H. Lee, J.-C. Nicolas & C. Quarta

Authors
  1. T. H. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J.-C. Nicolas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Quarta
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

THL, JCN, CQ wrote, revised, and amended the manuscript, JCN designed the graphic. CQ conceptualised the work and the ideas. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to C. Quarta.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This study does not contain any studies with animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, T.H., Nicolas, JC. & Quarta, C. Molecular and functional mapping of the neuroendocrine hypothalamus: a new era begins. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02411-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40618-024-02411-5

Keywords

Search

Navigation