Identifying mechanisms underlying sex differences in motoneuron discharge

项目摘要 神经生理学的研究历来将女性参与者排除在外。这导致了一口井 包括对男性运动的神经控制的理解，以及对 女性运动控制差异的机制。对女性运动的研究非常有必要 生理学，因为许多神经疾病的进展在性别之间有所不同。近年来，有研究表明， 包括足够数量的女性参与者发现了运动神经元的放电模式 神经肌肉疲劳在性别之间有所不同，但这些差异背后的机制尚不清楚。 来自脑干核团的下行单胺能传入提供和修饰运动神经元放电，并 在发动机系统中被广泛研究的不足。然而，我们的实验室已经开发出可靠的方法来量化这些 单胺能对人类运动神经元放电的影响。因此，要了解单胺能输入是否 负责运动神经元属性的性别差异，我将间接量化单胺能神经元的数量 雌性和雄性运动神经元的输入。 运动指令由兴奋、抑制和一种鲜为人知的神经调节成分组成 在它们随后的神经肌肉纤维的放电和激活中。神经调节是由释放引起的 两种单胺，5-羟色胺和去甲肾上腺素，从脑干到脊髓，基本上 改变运动神经元的放电模式。性激素对许多生理系统有广泛的影响。 存在于人体内，并存在性别差异。女性体内的雌二醇和孕酮水平会波动。 在月经周期中有规律的变化，这些波动与运动控制有关，包括 运动神经元的放电率和疲劳。此外，全身的神经元，包括脑干和 脊髓，含有雌二醇和黄体酮受体。这表明，波动的性激素可能 影响运动神经元的功能，但同样，潜在的机制还没有研究。因此，要准确地 评估运动神经元放电的性别差异，必须考虑激素周期。我会用表面肌电信号 用于量化自愿等长收缩期间运动神经元放电模式的阵列，以确定1)是否 运动神经元的单胺能输入不同于男性和女性；2)运动神经元是否有放电 女性的模式在月经周期中波动。 这项研究将评估单胺能传入运动神经元的数量是否在 性别测试已知性别差异的可能解释，同时也评估运动神经元的其他方面 出院。无论这些研究是否确定了性别差异，这项工作的发现不仅将进一步 关于这些性激素如何影响神经系统功能的科学知识，但将突出关键 出于需要、需要和公平考虑，对女性参与者进行额外研究的重要性。

Project Summary Studies in neurophysiology have historically excluded female participants. This has resulted in a well encompassing understanding of the neural control of movement in males, and a poor understanding of mechanisms underlying motor control differences in females. There is great need to study female motor physiology, as many neurological diseases progress differently between the sexes. In recent years, studies that have included adequate numbers of female participants have found motoneuronal discharge patterns and neuromuscular fatigue differ between the sexes but the mechanisms underlying these differences are unknown. Descending monoaminergic input from brainstem nuclei provide and modify motoneuronal discharge and is broadly understudied in the motor system. Our lab, however, has developed robust methods to quantify these monoaminergic influences on motoneuron discharge in humans. Thus, to understand if monoaminergic input is responsible for sex differences in motoneuron properties, I will indirectly quantify the amount of monoaminergic input to motoneurons in females and males. Motor commands consist of excitation, inhibition, and a lesser known neuromodulatory component that result in their subsequent discharge and activation of innervated muscle fibers. Neuromodulation is induced by release of two monoamines, serotonin and norepinephrine, from the brainstem to the spinal cord, which substantially alter discharge patterns of motoneurons. Sex hormones have extensive effects on many physiological systems in the human body and differ between the sexes. Females have levels of estradiol and progesterone that fluctuate regularly across the menstrual cycle and these fluctuations are associated with aspects motor control, including motoneuron discharge rates and fatigue. Additionally, neurons throughout the body, including the brainstem and spinal cord, contain estradiol and progesterone receptors. This suggests that fluctuating sex hormones may impact motoneuron function, but, again, underlying mechanisms have not been studied. Thus, to accurately assess sex differences in motoneuron discharge, hormonal cycles must be considered. I will use surface EMG arrays to quantify motoneuron discharge patterns during voluntary isometric contractions to determine 1) if monoaminergic input to motoneurons differs between males and females, and 2) whether motoneuron discharge patterns fluctuate across the menstrual cycle in females. This study will assess whether the amount of monoaminergic input motoneurons receive differs between the sexes to test a possible explanation for known sex differences, while also assessing other aspects of motoneuron discharge. Whether or not these studies identify sex-differences, findings from this work will not only further the scientific knowledge of how these sex hormones influence nervous system function but will highlight the critical importance for additional studies focusing on female participants out of need, necessity, and equity.