Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1(ARH)) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1(ARH) neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1(ARH) neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1(ARH) neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1(ARH) neurons. We propose that Kiss1(ARH) neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function.
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http://dx.doi.org/10.7554/eLife.16246 | DOI Listing |
Elife
January 2025
Department of Physiology, Development and Neuroscience, Downing site, University of Cambridge, Cambridge, United Kingdom.
The gonadotropin-releasing hormone (GnRH) neurons represent the key output cells of the neural network controlling mammalian fertility. We used GCaMP fiber photometry to record the population activity of the GnRH neuron distal projections in the ventral arcuate nucleus where they merge before entering the median eminence to release GnRH into the portal vasculature. Recordings in freely behaving intact male and female mice revealed abrupt ~8 min duration increases in activity that correlated perfectly with the appearance of a subsequent pulse of luteinizing hormone (LH).
View Article and Find Full Text PDFElife
January 2025
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
J Neurosci
January 2025
Laboratory of Reproductive Neurobiology, Hun-Ren Institute of Experimental Medicine, Budapest, 1083 Hungary;
While hypothalamic kisspeptin (KP) neurons play well-established roles in the estrogen-dependent regulation of reproduction, little is known about extrahypothalamic KP-producing (KP) neurons of the lateral septum. As established previously, expression in this region is low and regulated by estrogen receptor- and GABA receptor-dependent mechanisms. Our present experiments on knock-in mice revealed that transgene expression in the LS begins at P33-36 in females and P40-45 in males and is stimulated by estrogen receptor signaling.
View Article and Find Full Text PDFMetabolism
December 2024
Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC), Department of Cell Biology, Physiology and Immunology, University of Cordoba; and Hospital Universitario Reina Sofia, Cordoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:
Female reproduction is highly sensitive to body energy stores; persistent energy deficit, as seen in anorexia or strenuous exercise, is known to suppress ovulation via ill-defined mechanisms. We report herein that hypothalamic SIRT1, a key component of the epigenetic machinery that links nutritional status and puberty onset via modulation of Kiss1, plays a critical role in the control of the preovulatory surge of gonadotropins, i.e.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Laboratory of Reproductive Neurobiology, HUN-REN Institute of Experimental Medicine, Budapest, 1083 Hungary. Electronic address:
We developed a versatile 'IHC/LCM-Seq' method for spatial transcriptomics of immunohistochemically detected neurons collected with laser-capture microdissection (LCM). IHC/LCM-Seq uses aluminon and polyvinyl sulfonic acid for inventive RNA-preserving strategies to maintain RNA integrity in free-floating sections of 4% formaldehyde-fixed brains. To validate IHC/LCM-Seq, we first immunostained and harvested striatal cholinergic interneurons with LCM.
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