Institute of Physiology, Medical School, University of Pécs, Pécs, Hungary.
Centre for Neuroscience, Szentágothai Research Centre, Pécs, Hungary.
Front Endocrinol (Lausanne). 2023 Jan 4;13:993552. doi: 10.3389/fendo.2022.993552. eCollection 2022.
The striatum is an essential component of the basal ganglia that is involved in motor control, action selection and motor learning. The pathophysiological changes of the striatum are present in several neurological and psychiatric disorder including Parkinson's and Huntington's diseases. The striatal cholinergic neurons are the main regulators of striatal microcircuitry. It has been demonstrated that estrogen exerts various effects on neuronal functions in dopaminergic and medium spiny neurons (MSN), however little is known about how the activity of cholinergic interneurons are influenced by estrogens. In this study we examined the acute effect of 17β-estradiol on the function of striatal cholinergic neurons in adult mice . We also tested the effect of estrus cycle and sex on the spontaneous activity of cholinergic interneurons in the striatum. Our RNAscope experiments showed that ERα, ERβ, and GPER1 receptor mRNAs are expressed in some striatal cholinergic neurons at a very low level. In cell-attached patch clamp experiments, we found that a high dose of 17β-estradiol (100 nM) affected the spontaneous firing rate of these neurons only in old males. Our findings did not demonstrate any acute effect of a low concentration of 17β-estradiol (100 pM) or show any association of estrus cycle or sex with the activity of striatal cholinergic neurons. Although estrogen did not induce changes in the intrinsic properties of neurons, indirect effects modulation of the synaptic inputs of striatal cholinergic interneurons cannot be excluded.
纹状体是基底神经节的一个重要组成部分,参与运动控制、动作选择和运动学习。纹状体的病理生理变化存在于几种神经和精神障碍中,包括帕金森病和亨廷顿病。纹状体胆碱能神经元是纹状体微电路的主要调节者。已经证明,雌激素对多巴胺能和中型多棘神经元(MSN)中的神经元功能有多种影响,但是对于胆碱能中间神经元的活性如何受到雌激素的影响知之甚少。在这项研究中,我们检查了 17β-雌二醇对成年小鼠纹状体胆碱能神经元功能的急性影响。我们还测试了发情周期和性别对纹状体胆碱能中间神经元自发活动的影响。我们的 RNAscope 实验表明,ERα、ERβ 和 GPER1 受体 mRNA 以非常低的水平在一些纹状体胆碱能神经元中表达。在细胞贴附式膜片钳实验中,我们发现高剂量的 17β-雌二醇(100 nM)仅在老年雄性中影响这些神经元的自发放电率。我们的发现没有显示出低浓度 17β-雌二醇(100 pM)的任何急性作用,也没有显示发情周期或性别与纹状体胆碱能神经元活性之间的任何关联。尽管雌激素没有诱导神经元内在特性的变化,但不能排除间接影响纹状体胆碱能中间神经元突触输入的调制。