AAV MEDIATED TRANSFER OF V1A RECEPTOR GENE IN ADULT CNS

描述（申请人摘要）：神经肽表达与行为之间的关系是行为神经内分泌学中一个迅速发展的研究领域。精氨酸抗利尿激素参与许多社会行为，如社会识别、交际行为、攻击、亲代照顾和隶属关系。抗利尿激素受体在大脑中的分布在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，使研究人员能够实验地检查这种受体-行为关系。田鼠为抗利尿激素受体分布与社会行为之间的关系提供了一个很好的模型。例如，高度社会化、一夫一妻制的草原田鼠和不那么社会化、滥交的山地田鼠在受体分布和抗利尿激素调节的行为表达（配对结合、雄性间攻击和父系照顾）上都存在差异。本提案旨在开发一种技术，通过这种技术，人们可以实验地以组织特异性的方式操纵加压素受体在成年动物中的表达，并研究其行为后果。我们将开发两种含有抗利尿激素受体基因的腺相关病毒载体。基因表达在一个载体上由天然抗利尿激素受体启动子驱动，在另一个载体上由神经元特异性启动子驱动。这些载体将通过体外循环和特定部位注射，将抗利尿激素受体基因直接送入成人大脑，并使用受体结合试验评估其表达。区域特异性和时间方面的表达将进行检查。为了确定操纵抗利尿激素受体的表达是否会影响行为，将对动物进行一系列行为测试。在这个项目结束时，我们将对这项技术将为受体表达和行为关系的神经内分泌研究提供强大的新工具的程度有一个坚实的理解。这里创建的载体应该对其他物种的侵略研究有用。地盘行为和社会记忆。

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.