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We examined here the potential role of serotonin neurons in modulating the activity of the gonadotropin-releasing hormone (GnRH) pulse generator formed by the arcuate nucleus kisspeptin (ARNKISS) neurons. Acute brain slice electrophysiology revealed that \u223c60% of ARNKISS neurons in diestrous female mice were activated by serotonin while less than 10% were inhibited. Pharmacological studies indicated that combinatorial patterns of 5-HT receptor subtype activation were likely responsible for the excitatory actions. The role of serotonin in ARNKISS neuron synchronization behavior was assessed using GCaMP imaging in acute brain slices from diestrous female and male mice. In both sexes, serotonin-evoked potent recurring bouts of synchronization activity amongst ARNKISS neurons. To evaluate the impact of serotonin in vivo, we used \u201cfluidic\u201d GCaMP fiber photometry in which serotonin was infused directly into the ARN while recording the ARNKISS neuron population activity in freely behaving diestrous female mice. In all cases, the infusion of serotonin evoked a robust ARNKISS neuron synchronization episode. These data demonstrate that serotonin exerts a direct, predominantly stimulatory action on ARNKISS neuron pulse generator through a variety of 5-HT receptors. Serotonergic inputs appear to provide a potent synchronizing influence on the ARNKISS neuron population and suggest considerable potential for 5-HT to control the frequency of pulsatile reproductive hormone secretion in mice and likely other mammals.<\/jats:p>","DOI":"10.1210\/endocr\/bqag034","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:42:04Z","timestamp":1774615324000},"source":"Crossref","is-referenced-by-count":2,"title":["Robust serotonin activation of the kisspeptin GnRH pulse generator in male and female mice"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4554-2132","authenticated-orcid":false,"given":"Paul G","family":"Morris","sequence":"first","affiliation":[{"name":"Department of Physiology, Development and Neuroscience , Cambridge CB2 3EG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhuai","family":"Liu","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences , Dunedin 9054 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Birt","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience , Cambridge CB2 3EG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szilvia","family":"Vas","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience , Cambridge CB2 3EG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Ruiz Cruz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience , Cambridge CB2 3EG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Schafer","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences , Dunedin 9054 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H James","family":"McQuillan","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences , Dunedin 9054 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9615-3022","authenticated-orcid":false,"given":"Allan E","family":"Herbison","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience , Cambridge CB2 3EG ,","place":["UK"]},{"name":"Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences , Dunedin 9054 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"2026050604165474400_bqag034-B1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ejphar.2014.10.031","article-title":"Serotonin: a never-ending story","volume":"753","author":"Olivier","year":"2015","journal-title":"Eur J Pharmacol"},{"issue":"3","key":"2026050604165474400_bqag034-B2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3892\/br.2024.1816","article-title":"Effects of selective serotonin reuptake inhibitors on endocrine system (review)","volume":"21","author":"Ruiz-Santiago","year":"2024","journal-title":"Biomed Rep"},{"issue":"4","key":"2026050604165474400_bqag034-B3","first-page":"480","article-title":"Serotonin, a neurotransmitter involved in the regulation of luteinizing hormone release","volume":"14","author":"Vitale","year":"1993","journal-title":"Endocr Rev"},{"key":"2026050604165474400_bqag034-B4","first-page":"1621","volume-title":"The Physiology of Reproduction","author":"Kordon","year":"1994","edition":"2 ed"},{"key":"2026050604165474400_bqag034-B5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/B978-0-12-397175-3.00011-9","volume-title":"Knobil and Neill's Physiology of Reproduction. 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