Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females

Elife. 2018 Aug 6;7:e35656. doi: 10.7554/eLife.35656.


The neuropeptides tachykinin2 (Tac2) and kisspeptin (Kiss1) in hypothalamic arcuate nucleus Kiss1 (Kiss1ARH) neurons are essential for pulsatile release of GnRH and reproduction. Since 17β-estradiol (E2) decreases Kiss1 and Tac2 mRNA expression in Kiss1ARH neurons, the role of Kiss1ARH neurons during E2-driven anorexigenic states and their coordination of POMC and NPY/AgRP feeding circuits have been largely ignored. Presently, we show that E2 augmented the excitability of Kiss1ARH neurons by amplifying Cacna1g, Hcn1 and Hcn2 mRNA expression and T-type calcium and h-currents. E2 increased Slc17a6 mRNA expression and glutamatergic synaptic input to arcuate neurons, which excited POMC and inhibited NPY/AgRP neurons via metabotropic receptors. Deleting Slc17a6 in Kiss1 neurons eliminated glutamate release and led to conditioned place preference for sucrose in E2-treated KO female mice. Therefore, the E2-driven increase in Kiss1 neuronal excitability and glutamate neurotransmission may play a key role in governing the motivational drive for palatable food in females.

Keywords: 17-beta-estradiol; T-type calcium current; h-current; mouse; neuroscience; optogenetics; vGluT2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Calcium / metabolism
  • Calcium Channels, T-Type / genetics
  • Estradiol / administration & dosage
  • Estradiol / metabolism
  • Female
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / genetics
  • Kisspeptins / genetics*
  • Mice
  • Neurons / metabolism*
  • Neurons / pathology
  • Potassium Channels / genetics
  • Protein Precursors / genetics*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics
  • Tachykinins / genetics*
  • Vesicular Glutamate Transport Protein 2 / genetics*


  • Cacna1g protein, mouse
  • Calcium Channels, T-Type
  • Hcn1 protein, mouse
  • Hcn2 protein, mouse
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Kisspeptins
  • Potassium Channels
  • Protein Precursors
  • Slc17a6 protein, mouse
  • Tachykinins
  • Vesicular Glutamate Transport Protein 2
  • preprotachykinin
  • Estradiol
  • Calcium