Androgen modulation of vocal neurons

雄激素对发声神经元的调节

• 批准号: 7155507
• 负责人: AYAKO YAMAGUCHI
• 金额: $ 28.33万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155507
• 关键词: African; Androgens; Antiepileptic Agents; Behavior; Brain; Cell Nucleus; Data; Epilepsy; Female; Fire - disasters; Generations; Goals; Gonadal Steroid Hormones; Histological Techniques; In Vitro; Incidence; Injection of therapeutic agent; Ion Channel; Laryngeal Nerves; Larynx; Link; Membrane; Menstrual cycle; Modeling; Morphology; Motor; Motor Neurons; Motor output; Nerve; Neurons; Organ; Output; Patients; Pattern; Pharmaceutical Preparations; Population; Preparation; Production; Property; Rana; Rate; Research; Research Personnel; Role; Seizures; Shapes; Slice; Stereotyping; Steroids; System; Techniques; Testing; Testosterone; Therapeutic; Xenopus; Xenopus laevis; Xenopus sp.; awake; human disease; in vivo; male; neuromechanism; neuronal cell body; neuronal excitability; prevent; programs; relating to nervous system; research study; response; sex; size; steroid hormone; vocal control; vocalization

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.

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修改神经元和神经元回路的功能特性，以产生不同的性行为模式。在这个项目中，类固醇激素，神经元功能和行为之间的联系将通过使用非洲爪蛙的发声行为作为模型进行研究。 雄蛙和雌蛙产生不同性别的声音，由类固醇激素调节。雄性和雌性爪蟾的发声是由控制发声器官的喉运动神经元的性别特异性放电率产生的。因此，在这个系统中，理解行为的神经机制的挑战可以被简化为理解运动神经元产生定型的节律性尖峰模式的问题。拟议的研究将调查喉运动神经元和前运动神经元的生物物理和结构特性如何被类固醇激素修饰，以及这些变化如何帮助塑造性别特异性发声的运动输出。 最终，了解类固醇如何调节神经元的兴奋性将是重要的，在解开许多人类疾病的机制，包括癫痫等常见和重要的问题。最近的数据表明，某些类固醇可用作抗癫痫药物，而在某些患者中，类固醇激素明显增加癫痫发作的发生率。此外，癫痫发作可能与月经周期有关。然而，人们对类固醇如何诱导神经元之间突然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知之甚少。通过研究一个定义明确的神经系统，其中神经元的兴奋性明显受到雄激素的调节，如本文所提出的，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开发癫痫治疗方法的进一步进展是必要的。