Opus, sorry—I forgot to include the link to the paper! Here it is: www.cell.com/neuron/abstr...

Side note: The first author Teppei Goto has been a dedicated neuroendocrinologist specializing in kisspeptin. His previous work (elifesciences.org/articles/82533) explored menopause, this study tackles puberty—could the next installment complete a life-course trilogy on reproductive transitions?

PR from RIKEN www.riken.jp/press/2025/2... (Japanese only) ->
I would like to express my sincere thanks to Drs. Ken Murata (Univ. of Tokyo), Tomomi Karigo (Johns Hopkins), and Hiroko Sokumura (Nagoya Univ.) for their kind comments on the manuscript of this paper. (10/N

This study reveals a rapid regulatory mechanism in which AgRP neurons dynamically adjust reproductive timing in response to fluctuating food availability. How this "food-to-reproduction" circuit operates beyond the context of puberty remains an open question. (9/N

Conversely, partial ablation of AgRP neurons significantly increased kisspeptin pulsatility even under caloric restriction, allowing partial ovarian maturation. These findings establish AgRP neurons as key inhibitors of kisspeptin pulses, acting as a brake on puberty onset. (8/N

While all mice experienced their first estrus by P45 in the control group, only half reached puberty, and ovarian development was delayed, in the AgRP-activated group (C, D). (7/N

We then turned to AgRP neurons, key hunger sensors in the arcuate nucleus. AgRP neurons are known to be activated by fasting and rapidly suppressed by food availability. We found that artificially activating AgRP neurons blocked the surge in kisspeptin pulses even after refeeding (A, B). (6/N

Food scarcity is known to delay puberty, but how kisspeptin neurons sense metabolic status remains unclear. We found that under a mild caloric restriction suppressing puberty, low-frequency kisspeptin pulses persist. Once food availability was restored, pulsatile activity surged within hours. (5/N

Between P24 and P30, sharp peaks of pulsatile activity in kisspeptin neurons appeared. This activity preceded vaginal opening—the first visible sign of puberty—and increased in frequency with age. This provides definitive evidence that kisspeptin neuron pulses emerge before puberty onset. (4/N

Yet, due to technical challenges, the pulsatile activity of kisspeptin neurons in prepubertal animals remained uncharted. Using a genetic approach to express a Ca2+ sensor specifically in kisspeptin neurons, we successfully tracked their activity starting from P24 in mice. (3/N

An increase in the gonadotropin secretion rate drives sexual maturation. The master regulator of this rhythm is kisspeptin neurons in the hypothalamic arcuate nucleus. After maturity, these neurons fire in synchronized pulses every 30 min to 2 hrs, setting the pace for gonadotropin release. (2/N

Congratulations to Drs. Neyama and Cui on this fantastic publication!

Big congrats!

This research opens a new avenue of real-time, single-cell-level neuroendocrinology in freely behaving animals. We extend our heartfelt thanks to Drs. Tomomi Karigo and Takuya Osakada for their thoughtful comments on the manuscript! 7/