Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion
| Autor: | Timothy McLennan, Su Young Han, Katja Czieselsky, Allan E. Herbison |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty endocrine system Population Neuropeptide Biology Optogenetics Mice Kisspeptin Arcuate nucleus Internal medicine medicine Animals education Neurons education.field_of_study Kisspeptins Multidisciplinary Luteinizing hormone secretion Arcuate Nucleus of Hypothalamus Luteinizing Hormone Biological Sciences Gonadotropin secretion Mice Inbred C57BL Endocrinology Female Luteinizing hormone hormones hormone substitutes and hormone antagonists |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 112(42) |
| ISSN: | 1091-6490 |
| Popis: | Normal reproductive functioning in mammals depends upon gonadotropin-releasing hormone (GnRH) neurons generating a pulsatile pattern of gonadotropin secretion. The neural mechanism underlying the episodic release of GnRH is not known, although recent studies have suggested that the kisspeptin neurons located in the arcuate nucleus (ARN) may be involved. In the present experiments we expressed channelrhodopsin (ChR2) in the ARN kisspeptin population to test directly whether synchronous activation of these neurons would generate pulsatile luteinizing hormone (LH) secretion in vivo. Characterization studies showed that this strategy targeted ChR2 to 70% of all ARN kisspeptin neurons and that, in vitro, these neurons were activated by 473-nm blue light with high fidelity up to 30 Hz. In vivo, the optogenetic activation of ARN kisspeptin neurons at 10 and 20 Hz evoked high amplitude, pulse-like increments in LH secretion in anesthetized male mice. Stimulation at 10 Hz for 2 min was sufficient to generate repetitive LH pulses. In diestrous female mice, only 20-Hz activation generated significant increments in LH secretion. In ovariectomized mice, 5-, 10-, and 20-Hz activation of ARN kisspeptin neurons were all found to evoke LH pulses. Part of the sex difference, but not the gonadal steroid dependence, resulted from differential pituitary sensitivity to GnRH. Experiments in kisspeptin receptor-null mice, showed that kisspeptin was the critical neuropeptide underlying the ability of ARN kisspeptin neurons to generate LH pulses. Together these data demonstrate that synchronized activation of the ARN kisspeptin neuronal population generates pulses of LH. |
| Databáze: | OpenAIRE |
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