CONNECTIONS OF THE LIMBIC SYSTEM AND HYPOTHALAMUS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 拟议工作的长期目标是以高分辨率表征哺乳动物大脑中电路的结构和化学，这些电路是维持个体动物生存的基本驱动力的基础，并确保与饥饿和口渴，防御行为，生殖行为和睡眠/觉醒周期相关的物种的延续。以前的神经解剖学工作已经澄清了输入/输出关系和神经递质的内侧下丘脑子系统介导的这些广泛定义的功能，并已表明，他们与密切相关的边缘端脑区域的地形投影到外侧下丘脑区（LHA）。功能证据表明，LHA在正强化，行为唤醒和动机行为的各个方面起着重要作用，尽管其神经输入和轴突项目的地形组织知之甚少。拟议的工作是基于这样的假设，即LHA有两个功能和结构不同的区域相关的行为状态，和腹侧区被分为20个或更多个不同的细胞群或核相关的特定功能系统。本研究基于大鼠实验性神经解剖学方法，设计了三个具体目标来探讨这一假设：（1）将阐述基于连接和原位杂交相关mRNA表达的LHA分化的系统计算机图形图谱/数据库。(2)将确定并比较背侧和腹侧区域中细胞群的投影。和（3）在这些区域的神经元细胞类型（表型）将使用联合轴突运输/杂交组织化学方法来确定。这种分析/综合方法旨在为功能实验的合理设计提供一个结构框架，并为涉及前脑神经系统控制、饮食、攻击和防御生殖、睡眠-觉醒周期以及可能的情绪障碍的疾病提供新的见解和最终的治疗方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of the proposed work is to characterize at high resolution the structure and chemistry of circuits in the mammalian brain that underlie the basic drives that keep individual animals alive and assure perpetuation of the species associated with hunger and thirst, defensive behavior, reproductive behavior, and the sleep/wake cycle. Previous neuroanatomical work has clarified the input/output relationships and neurotransmitters of medial hypothalamic subsystems mediating each of these broadly defined functions, and has shown that they-along with closely associated limbic telencephalon regions-project topographically to the lateral hypothalamic area (LHA). Functional evidence suggests that the LHA plays an important role in positive reinforcement, behavioral arousal, and various aspects of motivated behavior, although the topographic organization of its neural inputs and axonal projects is poorly understood. The proposed work is based on the hypotheses that the LHA has two functionally and structurally distinct zones related to behavioral state, and the ventral zone being divided into 20 or more distinct cell groups or nuclei related to specific functional systems. Three specific aims based on the use of experimental neuroanatomical methods in the rat are designed to explore this hypotheses: (1) A systematic computer graphics atlas/database of LHA differentiation based on connections and in situ hybridization-related mRNA expression will be elaborated. (2) Projections of cell groups in the dorsal and ventral regions will be determined and compared. And (3) neuronal cell types (phenotypes) in these regions will be determined using combined axonal transport/hybridization histochemical methods. This analytical/synthetic approach is designed to provide a structural framework for the rational design of functional experiments, as well as provide new insights into, and eventually treatments for, diseases that involve forebrain neural systems controlling, eating, drinking, aggression and defense reproduction, the sleep-wake cycle, and presumably mood disorders as well.