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

Qiu, Jian; Rivera, Heidi M; Bosch, Martha A; Padilla, Stephanie L; Stincic, Todd L; Palmiter, Richard D; Kelly, Martin J; Rønnekleiv, Oline K · Elife · 2018

basic_science · Level V

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Abstract

The neuropeptides tachykinin2 (Tac2) and kisspeptin (Kiss1) in hypothalamic arcuate nucleus Kiss1 (Kiss1<sup>ARH</sup>) neurons are essential for pulsatile release of GnRH and reproduction. Since 17β-estradiol (E2) decreases <i>Kiss1 and Tac2</i> mRNA expression in Kiss1<sup>ARH</sup> neurons, the role of Kiss1<sup>ARH</sup> 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 Kiss1<sup>ARH</sup> neurons by amplifying <i>Cacna1g, Hcn1 and Hcn2</i> mRNA expression and T-type calcium and h-currents. E2 increased <i>Slc17a6</i> mRNA expression and glutamatergic synaptic input to arcuate neurons, which excited POMC and inhibited NPY/AgRP neurons via metabotropic receptors. Deleting <i>Slc17a6</i> 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.

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