Steroid-catecholamine-brain interactions in auditory-driven social behavior

描述（申请人提供）：包括多巴胺和去甲肾上腺素在内的儿茶酚胺系统是社会激励和奖励过程的基础，但相关研究几乎完全集中在中脑边缘多巴胺系统上，该系统影响对环境刺激的高度加工表征的行为反应。然而，还观察到脑干的感觉区域甚至听觉周边的儿茶酚胺投射，这表明社会激励过程可能开始于大脑听觉外围和初级感觉区域的反应性调节。大多数研究已经调查了类固醇调节酪氨酸羟化酶（TH），在儿茶酚胺合成的限速酶，都集中在雌激素替代对mesocorticolimbic多巴胺能系统的长期影响，但不是在初级感觉加工区。这个建议的目的是发现类固醇激素如何与儿茶酚胺相互作用的电路重要的正常神经驱动的社会行为的相互作用。通过采用一个简单但功能强大的脊椎动物模型系统，在一个强大的行为实验，涉及一个明确的反应，社会听觉刺激，激活特定的脑核同源神经化学物质的内容和连接到哺乳动物和人类将被分析。此外，通过循环类固醇激素的实验操作，将获得更好的了解类固醇，如雌激素，调节外周，初级和次级听觉处理中心内的儿茶酚胺。该研究的贡献有望为更好地了解社会听觉信号行为反应过程中儿茶酚胺能神经元的参与，以及中枢和外周听觉系统中儿茶酚胺的慢性和急性类固醇调节机制提供帮助。这一贡献将是重要的，因为它将成为未来研究的基础，这将提供对儿茶酚胺的作用及其在正常社会功能所需的脑回路中的类固醇调节的见解。在我们看来，所提出的项目是创新的，因为它采用了一个简单的脊椎动物模型系统，并具有测量一个明确的行为反应的一个重要的社会听觉刺激，是站不住脚的哺乳动物模型的优势。 公共卫生相关性：这些发现将有助于描述重要的，高度保守的神经化学物质，以及类固醇激素对它们的调节，在大脑回路中，这些神经化学物质是正确的大脑驱动的社会功能所必需的。这可能与人类疾病特别相关，如艾氏综合征和自闭症，其特征是对社会发声的定向不良。

DESCRIPTION (provided by applicant): Catecholamine systems, which include dopamine and noradrenaline, are fundamental to the processes of social incentive and reward, but relevant studies have focused almost exclusively on the mesolimbic dopamine system, which influences behavioral responses to highly processed representations of environmental stimuli However, catecholamine projections are also observed to sensory areas of the brainstem and even to the auditory periphery, suggesting that social incentive processes may begin with the modulation of responsiveness in the auditory periphery and primary sensory areas of the brain. Most studies that have investigated steroid regulation of tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis, have focused on long term effects of estrogen replacement on the mesocorticolimbic dopaminergic system, but not in primary sensory processing areas. The objective of this proposal is to discover how steroid hormones interact with catecholamines in circuits important for normal auditory-driven social behavioral interactions. By employing a simple but powerful vertebrate model system in a robust behavioral experiment that involves an unambiguous response to a social auditory stimulus, the activation of specific brain nuclei with homologous neurochemical contents and connections to mammals and humans will be analyzed. Furthermore, by experimental manipulation of circulating steroid hormones, a better understanding will be gained of how steroids, such as estrogen, regulate catecholamines within peripheral, primary and secondary auditory processing centers. The contribution of the proposed research is expected to provide a greater understanding of the involvement of catecholaminergic neurons during behavioral response to social auditory signals, and the mechanisms of chronic and acute steroid regulation of catecholamines in the central and peripheral auditory system. This contribution will be significant because it will become the foundation for future research that will provide insight to the role of catecholamines and their regulation by steroids in brain circuits required for normal social function. The proposed project is innovative, in our opinion, because it employs a simple vertebrate model system and has the advantage of measuring an unambiguous behavioral response to an important social auditory stimulus that is not tenable in mammalian models. PUBLIC HEALTH RELEVANCE: These findings will help delineate important, highly conserved neurochemicals, and their regulation by steroid hormones, in brain circuitry necessary for proper auditory-driven social function. This may be especially relevant to human disorders such as Asperger's syndrome and autism, which are characterized by poor orientation to social vocalizations.