The Neural Basis of Sexually Dimorphic Brain Function

性别二态性脑功能的神经基础

• 批准号: 6903435
• 负责人: Geert J. De Vries
• 金额: $ 12.22万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6903435
• 关键词: amygdala; animal developmental psychology; arginine vasopressin; behavior test; behavioral /social science research tag; child rearing; developmental neurobiology; gender difference; gene expression; hormone receptor; hormone regulation /control mechanism; in situ hybridization; ligands; maternal behavior; microinjections; neuroanatomy; neurotransmitters; parent offspring interaction; receptor expression; sex behavior; sex cycle; social behavior; testosterone; transfection /expression vector; vole

DESCRIPTION (provided by applicant): This is a proposal for a competing renewal of an Independent Scientist Award. The first four years of his award have allowed the PI to develop new lines of research, make substantial contributions to the discipline, and expand his research skills considerably. The PI proposes to continue these activities, now adding ligand binding assays and the use of viral vectors and other ways to modify gene expression in the brain to his array of skills. These are very powerful tools to analyze the molecular and cellular basis of behavior. The PI proposes to use these tools to study the functional significance of sex differences in vasopressin innervation of the brain. The central hypothesis driving this grant is that sex differences in neurotransmitter systems may induce sex differences in brain functions and behaviors as well as prevent them. The latter would occur to compensate for hormonal and physiological sex differences that might otherwise have caused undesirable sex differences. Parental behavior in rodents such as prairie voles, in which males as well as females care for the young, is a good example. Hormonal changes associated with pregnancy prime the brain of females for parental behavior. By necessity males must use a different strategy to be parental. This grant explores to what extent the sexually dimorphic vasopressin projections of the bed nucleus of the stria terminalis and amygdala help male and female voles to generate qualitatively similar parental behavior. These projections, which stimulate parental behavior in males, are much denser in males than in females. The plan is to study how vasopressin or its antagonists influence parental behavior at different stages of the reproductive cycle. The prediction is that interference with vasopressin transmission should cause sex differences in behaviors that otherwise are similar. A second aim is to study whether sex differences in these responses are caused by sex differences in gonadal hormone levels during development. A third aim is to study whether social conditions that minimize sex differences in parental behavior also change the involvement of vasopressin in parental behavior. Finally, experiments are planned to determine where in the brain vasopressin is likely to control parental behavior in a sexually dimorphic manner. Experiments will test whether social conditions that influence parental behavior change vasopressin receptor occupancy differently in males and females and whether changes in vasopressin receptor expression in turn influence parental behavior. By virtue of its theme, this project will increase what little knowledge is available on the neural control of paternal behavior as well as on the role of sex differences in the brain. Also, by showing that the effects of neuropeptides on behaviors are state- and sex-dependent, this study may affect drug therapies that are based on manipulating neurotransmission, because it underscores the notion that these therapies should be developed independently for men and women.

描述（由申请人提供）：这是一项独立科学家奖竞争性更新的提案。在获奖的头四年里，PI 能够开发新的研究领域，为学科做出重大贡献，并大大扩展他的研究技能。 PI 建议继续这些活动，现在将配体结合测定、病毒载体的使用以及其他改变大脑基因表达的方法添加到他的一系列技能中。这些是分析行为的分子和细胞基础的非常强大的工具。 PI 建议使用这些工具来研究大脑加压素神经支配中性别差异的功能意义。推动这项资助的核心假设是，神经递质系统中的性别差异可能会导致大脑功能和行为的性别差异，也可能会阻止这种差异。后者的发生是为了补偿荷尔蒙和生理上的性别差异，否则可能会导致不良的性别差异。草原田鼠等啮齿动物的父母行为就是一个很好的例子，其中雄性和雌性都会照顾幼崽。与怀孕相关的荷尔蒙变化使女性的大脑为父母行为做好准备。男性必须采用不同的养育策略。这项资助探讨了终纹和杏仁核床核的两性加压素投射在多大程度上帮助雄性和雌性田鼠产生性质相似的亲代行为。这些刺激男性父母行为的投射在男性中比在女性中更密集。该计划是研究加压素或其拮抗剂如何影响生殖周期不同阶段的父母行为。预测是，干扰加压素的传输会导致行为上的性别差异，否则这些行为是相似的。第二个目的是研究这些反应中的性别差异是否是由发育过程中性腺激素水平的性别差异引起的。第三个目的是研究最小化父母行为性别差异的社会条件是否也会改变加压素在父母行为中的参与。最后，计划进行实验以确定大脑中加压素可能以性别二态性方式控制父母行为的位置。实验将测试影响父母行为的社会条件是否会以不同方式改变男性和女性的加压素受体占用率，以及加压素受体表达的变化是否反过来影响父母行为。凭借其主题，该项目将增加关于父亲行为的神经控制以及性别差异在大脑中的作用的现有知识。此外，通过表明神经肽对行为的影响是状态和性别依赖性的，这项研究可能会影响基于操纵神经传递的药物疗法，因为它强调了这些疗法应该为男性和女性独立开发的概念。