Amygdala Kisspeptin Neurons: Putative Mediators of Olfactory Control of the Gonadotropic Axis

Pineda, Rafael; Plaisier, Fabrice; Millar, Robert P.; Ludwig, Mike

doi:10.1159/000445895

Cited by 82 publications

(106 citation statements)

References 71 publications

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“…Our data are supported by anatomical tracing studies that show the AOB provides dense input to all three MeA subdivisions [34], but neurons sensitive to volatile molecules which induce reproductive neuroendocrine effects (oestrous induction, puberty acceleration or delay) terminate principally in the MeApd [35, 36]. Reciprocal connections between MeApd MeA Kiss neurons and the anterior AOB have been identified previously [14], suggesting that these neurons are directly targeted by pheromonal pathways but also may feedback to the AOB. When the overall number of c-Fos + neurons in the MeA was compared to the number of c-Fos + MeA Kiss (tdTomato + ) neurons (online suppl.…”

Section: Discussionsupporting

confidence: 86%

“…Although activation of the MeA in response to opposite-sex chemosensory cues has been reported previously [8, 32], the specific neural circuit underlying the reproductive endocrine response remains poorly defined. Due to the recently revealed connectivity of MeA Kiss neurons with the AOB and GnRH neurons [14], we hypothesized that MeA Kiss neurons process sexually relevant olfactory stimuli to regulate reproductive neuroendocrine function. Male mice are preferentially attracted to ovary-intact females in proestrous and oestrous stages [33], therefore urine used as a chemosensory stimulus was collected from ovary-intact females primarily from proestrous and oestrous stages.…”

Section: Discussionmentioning

confidence: 99%

“…MeA Kiss neurons are reciprocally connected to the AOB and a subset of MeA Kiss neurons contact GnRH neurons in the POA [14]. Chemogenetic activation of MeA Kiss neurons reduces anxiety and enhances the preference for oestrous females in male mice [15].…”

Section: Introductionmentioning

confidence: 99%

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Medial Amygdala Kiss1 Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

et al. 2018

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Background/Aims: The medial amygdala (MeA) responds to olfactory stimuli and alters reproductive physiology. However, the neuronal circuit that relays signals from the MeA to the reproductive axis remains poorly defined. This study aimed to test whether MeA kisspeptin (MeA^Kiss) neurons in male mice are sensitive to sexually relevant olfactory stimuli and transmit signals to alter reproductive physiology. We also investigated whether MeA^Kiss neurons have the capacity to elaborate glutamate and GABA neurotransmitters and potentially contribute to reproductive axis regulation. Methods: Using female urine as a pheromone stimulus, MeA^Kiss neuronal activity was analysed and serum luteinizing hormone (LH) was measured in male mice. Next, using a chemogenetic approach, MeA^Kiss neurons were bi-directionally modulated to measure the effect on serum LH and evaluate the activation of the preoptic area. Lastly, using in situ hybridization, we identified the proportion of MeA^Kiss neurons that express markers for GABAergic (Vgat) and glutamatergic (Vglut2) neurotransmission. Results: Male mice exposed to female urine showed a two-fold increase in the number of c-Fos-positive MeA^Kiss neurons concomitant with raised LH. Chemogenetic activation of MeA^Kiss neurons significantly increased LH in the absence of urine exposure, whereas inhibition of MeA^Kiss neurons did not alter LH. In situ hybridization revealed that MeA^Kiss neurons are a mixed neuronal population in which 71% express Vgat mRNA, 29% express Vglut2 mRNA, and 6% express both. Conclusions: Our results uncover, for the first time, that MeA^Kiss neurons process sexually relevant olfactory signals to influence reproductive hormone levels in male mice, likely through a complex interplay of neuropeptide and neurotransmitter signalling.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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Medial Amygdala Kiss1 Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

et al. 2018

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“…Kiss1 mRNA has also been identified in the rodent amygdala where its expression is positively modulated by gonadal sex steroids [21,22]. Other brain regions demonstrating Kiss1r expression include the habenula, thalamus, hippocampus, and the olfactory system [15,23,24]. In humans, KISS1 and KISS1R mRNA has been identified outside the hypothalamus in the amygdala, caudate, cingulate, globus pallidus, hippocampus, medial and superior frontal gyrus, nucleus accumbens, parahippocampal gyrus, substantia nigra, putamen, and thalamus in varying degrees [19,20].…”

Section: Kisspeptin Signalling Outside the Hypothalamusmentioning

confidence: 99%

“…Recently, an anatomical framework for kisspeptin's role in olfaction has been identified in rodents involving the amygdala, which is a central structure in the olfactory system [24]. Using microinjections of retro-and anterograde tracers, neuronal connections were observed between the acces-sory olfactory bulb and kisspeptin neurones within the amygdala with these latter neurones also projecting via the stria terminalis to GnRH neurones in the preoptic area [24].…”

Section: Kisspeptin and Olfactionmentioning

confidence: 99%

Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Comninos

Dhillo

2017

Neuroendocrinology

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The emergence of kisspeptin as a crucial regulator of the hypothalamo-pituitary-gonadal (HPG) axis over the last 14 years has answered many questions as to the control of reproductive hormone secretion from the hypothalamus. More recently, the role of kisspeptin outside the HPG axis has received increasing attention in the hope of delineating the pathways linking various sensory and social behaviours to reproduction. These studies, in a range of species from zebrafish to humans, have identified a role for kisspeptin in behavioural networks related to reproduction including olfaction, audition, fear, anxiety, mood, and sexual arousal. The available evidence suggests that extrahypothalamic kisspeptin signalling encourages positive aspects of emotional and sexual brain processing in a presumed drive towards reproduction and ultimately maintenance of the species at a population level. In this review, we examine these studies, which collectively propose that kisspeptin may integrate sexual and emotional brain processing with the control of the HPG axis.

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Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder

et al. 2022

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ImportanceDespite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown.ObjectiveTo test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD.Design, Setting, and ParticipantsThis randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021.InterventionsA 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.Main Outcomes and MeasuresBlood oxygen level–dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli.ResultsOf the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P &lt; .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin’s enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects.Conclusions and RelevanceThese findings lay the foundations for clinical applications for kisspeptin in women with HSDD.Trial RegistrationISRCTN trial registry identifier: ISRCTN17271094

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Amygdala Kisspeptin Neurons: Putative Mediators of Olfactory Control of the Gonadotropic Axis

Cited by 82 publications

References 71 publications

Medial Amygdala <b><i>Kiss1</i></b> Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

Medial Amygdala <b><i>Kiss1</i></b> Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder

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