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）：这是对独立科学家奖的竞争更新的建议。他奖项的前四年使PI能够开发新的研究线，对学科做出了重大贡献，并大大扩展了他的研究技能。 PI建议继续这些活动，现在添加配体结合测定，并使用病毒载体以及其他方法将大脑中基因表达的方法修改为他的技能。这些是分析行为的分子和细胞基础的非常强大的工具。 PI建议使用这些工具研究大脑加压素神经支配中性别差异的功能意义。推动这笔赠款的中心假设是，神经递质系统的性别差异可能引起大脑功能和行为的性别差异，并预防它们。后者将发生弥补激素和生理性别差异，否则可能导致不良的性别差异。一个很好的例子是啮齿动物的父母行为，例如，雄性和女性照顾年轻的雄性和女性。与怀孕有关的荷尔蒙变化是女性的大脑，以实现父母行为。必要时，男性必须使用不同的策略才能成为父母。该赠款探讨了层末端和杏仁核的床核的性二态加压素的投影在多大程度上有助于雄性和女性产生质量上相似的父母行为。这些刺激男性父母行为的预测在男性中比女性更浓。该计划是研究加压素或其拮抗剂如何在生殖周期的不同阶段影响父母的行为。预测是，干扰加压素传播应在否则相似的行为上引起性别差异。第二个目的是研究这些反应中的性别差异是否是由于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，以确定脑血管加压素在脑血管加压素中可能以性二态性方式控制父母的行为。实验将测试影响父母行为的社会条件是否改变了男性和女性的加压素受体占用率是否不同，以及加压素受体表达的变化是否会影响父母的行为。由于其主题，该项目将增加有关父亲行为神经控制以及性别差异在大脑中的作用的知识。同样，通过证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独立开发男人和女性的疗法。