The role of the amygdala in modulating reproduction

项目总结 生殖和青春期的开始是由下丘脑-垂体-性腺(HPG)轴调节的，但尽管 许多研究表明，调节HPG轴的机制以及破坏HPG轴的机制还不完全。 明白了。到目前为止，大多数研究主要集中在下丘脑内的机制上 调节HPG轴，很少关注下丘脑以外的区域如何调节生殖。 杏仁核位于内侧颞叶和杏仁内侧核(Mea)，有 许多行为和生理功能，包括对青春期和生殖生理的影响。 然而，mea调节青春期开始和生殖的机制是完全 未知。神经肽Kispeptin通过激活GnRH神经元来调节生殖。接吻 神经元在几个不同的大脑区域被检测到，主要是下丘脑和Mea，但调节 而且，Kispeptin在MEA中的作用还知之甚少。因此，kispeptin在mea中可能是其中之一 杏仁核调节生殖的机制。目标1将研究Kispeptin在 MEA通过以下方式调节生殖：1)检测MEA Kiss1神经元可能的生殖功能。 通过选择性地破坏或激活Mea Kiss1神经元成为成年期；2)鉴定 Mea Kiss1神经元，以了解Kispeptin神经元中还产生了哪些其他信号因子 作为mea Kiss1神经元中的识别受体，可能有助于深入了解这些神经元是如何调控的；3) 通过确定是否有神经投射，检查Mea区可能如何与HPG轴“对话” 从MEA到下丘脑Kiss1和GnRH神经元。像Kispeptin一样，谷氨酸和GABA神经元 在MEA中也高表达，并已被证明调节青春期，涉及谷氨酸和GABA 作为MEA调节青春期的额外机制。目标2侧重于1)GABA在 前MEA和2)后MEA中的谷氨酸和Kispeptin，在调节青春期启动中的作用。它也是 目前尚不清楚MEA是否像在男性中那样调节成年生殖和青春期开始 女性，这项建议将检查男性和女性，以确定任何性别差异，特别是 因为青春期的开始是性二态的(女性早于男性)。总而言之，这项建议旨在 确定MEA调节生殖的分子机制(S)和特定细胞类型 内分泌学。这项工作可能为不孕不育的治疗提供重要的新信息， 无排卵、特发性低促性腺激素减退和闭经 与杏仁核功能异常相关的疾病的生殖生理，如自闭症和 精神分裂症。已知MEA还调节许多情绪和生理状态，因此， 这个项目可能会为社会信息如何调节生殖生理提供新的见解。

PROJECT SUMMARY Reproduction and puberty onset are regulated by the hypothalamic-pituitary-gonadal (HPG) axis, but despite much research, the mechanisms that can modulate the HPG axis, as well as disrupt the HPG axis, are not fully understood. To date, most research has focused primarily on the mechanisms within the hypothalamus that regulate the HPG axis, with little focus on how extra-hypothalamic brain regions may modulate reproduction. The amygdala is located in the medial temporal lobe and the medial nucleus of the amygdala (MeA), has numerous behavioral and physiological functions, including effects on puberty and reproductive physiology. However, the mechanisms by which the MeA modulates puberty onset and reproduction are completely unknown. The neuropeptide kisspeptin regulates reproduction by activating GnRH neurons. Kisspeptin neurons are detected in several discrete brain areas, primarily the hypothalamus and MeA, but the regulation and function of kisspeptin in the MeA is poorly understood. Thus, kisspeptin in the MeA may be one mechanism by which the amygdala modulates reproduction. Aim 1 will examine the role of kisspeptin in the MeA’s modulation of reproduction by: 1) examining possible reproductive functions of MeA Kiss1 neurons in adulthood by selectively destroying or activating MeA Kiss1 neurons; 2) identify the molecular phenotype of MeA Kiss1 neurons to understand what other signaling factors, if any, are made in kisspeptin neurons, as well as identify receptors in MeA Kiss1 neurons that may give insight into how these neurons are regulated; 3) examine how the MeA region may be “talking” to the HPG axis by determine if there are neural projections from the MeA to hypothalamic Kiss1 and GnRH neurons. Like kisspeptin, glutamate and GABA neurons are also highly expressed in the MeA and have been shown to regulate puberty, implicating glutamate and GABA as additional mechanisms by which the MeA may modulate puberty. Aim 2 focuses on the role of 1) GABA in the anterior MeA and 2) glutamate and kisspeptin in the posterior MeA, in regulating puberty onset. It is also currently unknown whether the MeA modulates adult reproduction and puberty onset in males as it does in females, and this proposal will examine both males and females to identify any sex differences, especially since puberty onset is sexually dimorphic (females earlier than males). In summary, this proposal seeks to identify the molecular mechanism(s) and specific cell types involved in the MeA’s modulation of reproductive endocrinology. This work may provide important novel information relevant to treatments in infertility, anovulation, idiopathic hypogonadotropic hypogonadism, and amenorrhea, as well as understanding reproductive physiology in disorders associated with aberrant amygdala function, such as autism and schizophrenia. The MeA is also known to modulate numerous emotions and physiological states and therefore, this project may provide new insight regarding how social information modulates reproductive physiology.