AAV MEDIATED TRANSFER OF V1A RECEPTOR GENE IN ADULT CNS

描述(申请人摘要)：神经肽表达和行为之间的关系是行为神经内分泌学中一个迅速扩展的研究领域。精氨酸加压素参与许多社会行为，如社会认可、交流行为、攻击性、父母关爱和亲子关系。加压素受体在大脑中的分布在具有不同社会行为的物种之间差异很大。迫切需要一种特定的技术，使研究人员能够从实验上检验这种受体-行为关系。田鼠为研究加压素受体分布和社会行为之间的关系提供了一个很好的模型。例如，高度社会性、一夫一妻制的草原田鼠和较少社会性、混交的山地田鼠在受体分布和受加压素调节的行为(配对、雄性间攻击性和父亲关怀)的表达上都不同。这项提议旨在开发一种技术，通过这种技术，人们可以通过组织特异性的方式在成年动物身上实验性地操纵加压素受体的表达，并研究其行为后果。我们将开发两个含有加压素受体基因的腺相关病毒载体。一个载体中的基因表达将由天然的加压素受体启动子驱动，另一个载体中的基因表达将由神经元特异性启动子驱动。这些载体将被用来通过静脉注射将加压素受体基因直接输送到成人大脑中。和部位特异性注射，并将使用受体结合分析来评估表达。将检查表达的地区性和时间性方面。为了确定操纵加压素受体表达是否会影响行为，动物将接受一系列行为测试。在这个项目的结束时，我们将对这项技术将在多大程度上为神经内分泌研究受体表达和行为的关系提供一个强大的新工具有一个坚实的理解。这里创建的媒介应该对其他物种的攻击性研究有用。领地行为和社会记忆。

DESCRIPTION (applicant's abstract): The relationship between neuropeptide expression and behavior is a rapidly expanding area of research within behavioral neuroendocrinology. Arginine vasopressin is involved in a number of social behaviors, such as social recognition, communicative behaviors, aggression, parental care and affiliation. The distribution of vasopressin receptors in the brain varies greatly among species with different social behaviors. There is a compelling need for a specific technique which will allow researchers to experimentally examine this receptor-behavior relationship. Voles provide an excellent model for the relationship between vasopressin receptor distribution and social behavior. For example, the highly social, monogamous prairie voles and the less social, promiscuous montane vole differ both in receptor distribution and the expression of behaviors regulated by vasopressin (pair-bonding, inter-male aggression, and paternal care). This proposal is designed to develop a technique by which one can experimentally manipulate vasopressin receptor expression in adult animals in a tissue-specific manner and investigate the behavioral consequences. We will develop two adeno-associated virus vectors containing the vasopressin receptor gene. Gene expression in one vector will be driven by the native vasopressin receptor promoter and in the other by a neuron- specific promoter. These vectors will be used to deliver the vasopressin receptor gene directly into the adult brain, via i.c.v. and site specific injections, and expression will be assessed using receptor binding assays. The regional specificity and temporal aspects of expression will be examined. To determine whether manipulating vasopressin receptor expression will affect behavior, animals will be subjected to a series of behavioral tests. At the conclusion of this project we will have a solid understanding of the degree to which this technology will provide a powerful new tool for neuroendocrine studies of the relationship of receptor expression and behavior. The vectors created here should be useful in other species for the study of aggression. territorial behavior and social memory.