Androgen modulation of vocal neurons

描述(由申请人提供)：拟议项目的长期目标是了解类固醇激素如何改变神经元和神经元回路的功能属性，以产生不同于性别的行为模式。在这个项目中，将以非洲爪蛙的发声行为为模型，研究类固醇激素、神经功能和行为之间的联系。 雄性和雌性青蛙产生性别上不同的发声，这是由类固醇激素调节的。雄性和雌性非洲爪哇的发声是由控制发声器官的喉部运动神经元的性别特异性放电频率产生的。因此，在这个系统中，理解行为的神经机制的挑战可以归结为理解运动神经元产生刻板印象的节律性尖峰模式的问题。这项拟议的研究将调查类固醇激素如何改变喉运动神经元和运动前神经元的生物物理和结构特性，以及这些变化如何帮助塑造构成特定性别发声的运动输出。 最终，了解类固醇如何调节神经元的兴奋性，对于解开许多人类疾病的机制将是重要的，包括癫痫等常见而重要的问题。最近的数据表明，某些类固醇可能被用作抗癫痫药物，而在一些患者中，类固醇激素明显增加了癫痫发作的发生率。此外，癫痫发作可能与月经周期有关。然而，关于类固醇如何在神经元之间诱导突然的同步放电导致癫痫发作，以及如何使用它们来防止这种活动风暴，人们知之甚少。通过研究一个明确定义的神经系统，其中神经元的兴奋性明显地受到雄激素的调节，我们可以更好地理解触发神经元活动爆发的细胞机制。这种对细胞活动的更详细的了解对于在开发癫痫治疗方法方面取得进一步进展是必要的。

DESCRIPTION (provided by applicant): The long-term goal of the proposed project is to understand how steroid hormones modify the functional properties of neurons and neuronal circuits to produce sexually distinct behavior patterns. In this project, the link between steroid hormones, neuronal function, and behavior will be investigated by using the vocal behavior of the African clawed frog as a model. Male and female frogs produce sexually distinct vocalizations that are regulated by steroid hormones. The vocalizations of male and female Xenopus are produced by the sex-specific firing rates of laryngeal motoneurons that control the vocal organ. Thus, in this system, the challenge of understanding the neural mechanisms of behavior can be reduced to a problem of understanding generation of stereotyped rhythmic spike patterns by motoneurons. The proposed research will investigate how biophysical and structural properties of laryngeal motoneurons and premotor neurons are modified by steroid hormones, and how these changes help shape the motor output that underlies sex-specific vocal production. Ultimately, understanding how steroids modulate the excitability of neurons will be important in unraveling the mechanisms of numerous human diseases including such common and important problems as epilepsy. Recent data suggests that certain steroids may be used as anti-epileptic drugs while in some patients, steroid hormones clearly increase the incidence of epileptic seizure. In addition, seizures can be linked to the menstrual cycle. However, there is very little known about how steroids can induce a sudden synchronous firing among neurons that causes seizure nor how they can be used to prevent such a storm of activity. By studying a well-defined neural system in which neuronal excitability is clearly regulated by androgen, as proposed here, we can better understand the cellular mechanisms that trigger bursts of neuronal activity. This more detailed understanding of cellular activity is necessary for further progress to be made in developing therapeutic approaches to epilepsy.