Estrogen Signaling in Nucleus Accumbens Astrocytes

项目总结 星形胶质细胞已被证明在突触传递中发挥重要作用。在出现的时候 关于神经递质对星形胶质细胞的影响的研究，关于其他信号如何 激素等分子会影响星形胶质细胞的信号传递。一种被广泛研究的重要荷尔蒙 神经信号转导是雌二醇(E2)。这与药物等动机行为有重要关系。 星形胶质细胞信号和雌激素信号影响药物寻求行为的成瘾。然而，它是 不知道雌激素是如何特别影响星形胶质细胞信号的。这项提案将决定雌激素如何 影响星形胶质细胞信号及其随后对三方突触传递的调节。对于这项建议，我 将重点放在伏隔核(NAC)的星形胶质细胞上，因为这一大脑区域对药物寻找至关重要 表现出结构和功能上的性别差异。我假设雌二醇会增加细胞内 通过与星形胶质细胞上的雌激素受体结合，星形胶质细胞中的钙离子。这种受体结合将导致 神经胶质递质释放，进而增加兴奋性突触传递。对于这个检验假说，我会 使用双光子显微镜检查星形胶质细胞的钙活性。我首先要确定的是雌二醇量增加 NAC星形胶质细胞的钙活性(目标1a)。然后我会确定位置和ER亚型以及细胞 表达ER的类型(目标1b)。对于目标2，我将测试E2对兴奋性突触的影响 变速箱。首先，我将通过测量向内缓慢的速度来确定E2在哪里刺激神经胶质递质的释放 电流，星形细胞谷氨酸释放的生物测定(目标2a)。此外，我还将监控兴奋性岗位 突触电流(EPSCs)，并确定负责EPSCs变化的神经胶质递质(目标2b)。这 该提案将填补雌激素如何影响星形胶质细胞信号传递的知识空白，这可能导致进一步 了解新来港儿童相关行为的性别差异。这项建议还将使我能够掌握许多 双光子钙成像和电生理学等研究技术将促进我的 职业目标是成为一名独立的学术神经科学研究人员。

PROJECT SUMMARY Astrocytes have been shown to play an important role in synaptic transmission. While there is emerging research about the effects of neurotransmitters on astrocytes, there is little known about how other signaling molecules such as hormones impact astrocyte signaling. One important hormone that is well studied with neuronal signaling is estradiol (E2). This has important relevance in motivated behaviors such as drug addiction where astrocyte signaling and estrogen signaling affect drug seeking behavior. However, it is unknown how estrogen specifically affects astrocyte signaling. This proposal will determine how estrogen affects astrocyte signaling and its subsequent regulation of tripartite synaptic transmission. For this proposal, I will focus on astrocytes in the nucleus accumbens (NAc) as this brain region is critical for drug seeking behaviors and displays structural and functional sex differences. I hypothesize that E2 will increase intracellular calcium in astrocytes by binding to estrogen receptors on astrocytes. This receptor binding will lead to gliotransmitter release which will in turn increase excitatory synaptic transmission. To this test hypothesis, I will use two photon microscopy to examine calcium activity in astrocytes. I will first establish that E2 increases calcium activity in NAc astrocytes (Aim 1a). I will then determine the location and ER subtype as well as cell type in which ER is expressed (Aim 1b). For Aim 2, I will test the effects of E2 on excitatory synaptic transmission. First, I will determine where E2 stimulates gliotransmitter release by measuring slow inward currents, a biological assay of astrocytic glutamate release (Aim 2a). In addition, I will monitor excitatory post synaptic currents (EPSCs) and determine the gliotransmitter responsible for changes in EPSCs (Aim 2b). This proposal will fill the knowledge gap of how estrogen affects astrocyte signaling which could lead to further understanding of sex differences in NAc related behaviors. This proposal will also allow me to master many research techniques such as two photon calcium imaging as well as electrophysiology, which will promote my career goals to become an independent academic neuroscience researcher.