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

听觉驱动的社会行为中类固醇-儿茶酚胺-大脑的相互作用

• 批准号: 8268193
• 负责人: PAUL M. FORLANO
• 金额: $ 15.7万
• 依托单位: BROOKLYN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8268193
• 关键词: Acute; Adrenergic Receptor; Animals; Area; Asperger Syndrome; Attention; Auditory; Auditory Physiology; Auditory system; Autistic Disorder; Bass; Behavior; Behavioral; Biological Models; Brain; Brain Diseases; Brain Stem; Catecholamines; Cell Nucleus; Cells; Chronic; Collaborations; Cues; Data; Disease; Dopamine; Dopamine Receptor; Dopaminergic Cell; Ear; Enzymes; Estrogen Replacements; Estrogens; Exhibits; Exposure to; Female; Fishes; Foundations; Funding; Future; Human; Hypothalamic structure; Incentives; Labyrinth; Long-Term Effects; Mammals; Measures; Midbrain structure; Modeling; Neurons; Norepinephrine; Patient currently pregnant; Peripheral; Phenotype; Population; Preoptic Areas; Process; Prosencephalon; Regulation; Research; Rewards; Role; Sensory; Sensory Process; Signal Pathway; Signal Transduction; Social Behavior; Social Functioning; Social Interaction; Source; Steroid Receptors; Steroids; Stimulus; Substantia nigra structure; System; Testing; Tyrosine 3-Monooxygenase; United States National Institutes of Health; Ventral Tegmental Area; Vertebrates; Work; auditory nuclei; auditory pathway; auditory stimulus; basal forebrain; behavior influence; hormone regulation; innovation; insight; locus ceruleus structure; male; mesolimbic system; nerve supply; neurochemistry; noradrenergic; pars compacta; receptor; research study; response; reward circuitry; social; sound; steroid hormone; vocalization

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.

描述（由申请人提供）：儿茶酚胺系统，包括多巴胺和去甲肾上腺素，是社会激励和奖励过程的基础，但相关研究几乎只关注中脑边缘多巴胺系统，该系统影响对环境刺激的高度加工表征的行为反应。然而，儿茶酚胺投射也被观察到脑干的感觉区域，甚至听觉外围。提示社会激励过程可能开始于大脑听觉外围区和初级感觉区的反应调节。大多数研究类固醇调节酪氨酸羟化酶（TH）（儿茶酚胺合成中的限速酶）的研究都集中在雌激素替代对中皮质边缘多巴胺能系统的长期影响上，而不是在初级感觉加工区域。本提案的目的是发现类固醇激素如何与儿茶酚胺在正常听觉驱动的社会行为互动的重要电路中相互作用。通过使用一个简单但强大的脊椎动物模型系统，在一个强大的行为实验中，涉及对社会听觉刺激的明确反应，将分析具有同源神经化学内容和与哺乳动物和人类联系的特定脑核的激活。此外，通过对循环类固醇激素的实验操作，将更好地了解类固醇（如雌激素）如何调节周围、初级和次级听觉处理中心的儿茶酚胺。本研究的贡献有望为儿茶酚胺能神经元参与社会听觉信号的行为反应提供更好的理解，以及儿茶酚胺在中枢和外周听觉系统中慢性和急性类固醇调节的机制。这一贡献将是重要的，因为它将成为未来研究的基础，这些研究将深入了解儿茶酚胺的作用，以及它们在正常社会功能所需的脑回路中由类固醇调节的作用。在我们看来，拟议的项目是创新的，因为它采用了一个简单的脊椎动物模型系统，并且具有测量对重要的社会听觉刺激的明确行为反应的优势，这在哺乳动物模型中是站不住脚的。