In female mice, the brain cells that trigger puberty (Kiss1 neurons) change how they fire electrical signals as the animal matures. Before puberty they fire only short bursts, but after puberty they can keep firing steadily, which is needed to start the hormone cascade for reproduction. This shift depends on estrogen and involves many ion‑channel genes turning on or off.

Puberty is a critical transition period to achieve reproductive capacity in all mammalian species. At puberty, hypothalamic <i>Kiss1</i> neurons release kisspeptin, stimulating gonadotropin-releasing hormone (GnRH) release and activating the hypothalamic-pituitary-gonadal (HPG) axis. Here, we show that <i>Kiss1</i> neurons in the arcuate nucleus of the hypothalamus (<i>Kiss1^ARC</i>) of female mice undergo profound intrinsic plasticity at puberty. <i>Kiss1^ARC</i> neurons in brain slices from 3-wk-old mice, when depolarized, typically fire a short high-frequency burst of action potentials before falling silent. This would make them unsuitable for the sustained activity that is required to activate pulsatile GnRH secretion and the HPG axis. At 4 wk of age and after puberty, <i>Kiss1^ARC</i> neurons can fire a sustained train of action potentials. There is a concomitant hyperpolarization in action potential threshold and postspike minimum voltage and larger medium after-hyperpolarizations (mAHP) and hyperpolarization-induced voltage sags. Transcriptomic profiling showed significant changes in ion channel expression after puberty. Using quantitative PCR, we confirmed changes in genes encoding voltage-gated sodium, calcium, potassium, and cation channels. Blocking hyperpolarization-induced cation channels caused <i>Kiss1^ARC</i> neurons from postpuberty mice to fire less sustained trains of action potentials. Recordings from <i>Kiss1^ARC</i> neurons in mice after ovariectomy and 17&#x3b2;-estradiol replacement revealed a critical window of estrogen-dependent plasticity between 3 and 6 wk, which is essential for the maturation of <i>Kiss1^ARC</i> neurons and the development of their adult electrophysiological activity. This represents an example of sex steroid-dependent plasticity in the mammalian brain at puberty.