CONNECTIONS OF THE LIMBIC SYSTEM AND HYPOTHALAMUS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项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成分，这些电路是维持单个动物存活的基本驱动力，并确保与饥饿和口渴、防御行为、生殖行为和睡眠/清醒周期相关的物种永久化。先前的神经解剖学工作已经阐明了调节这些广义功能的下丘脑内侧亚系统的输入/输出关系和神经递质，并表明它们与密切相关的边缘端脑区在地形上投射到下丘脑外侧区(LHA)。功能证据表明，LHA在积极强化、行为唤醒和动机行为的各个方面发挥着重要作用，尽管其神经输入和轴突投射的地形图组织尚不清楚。这项工作是基于这样的假设：LHA有两个与行为状态相关的功能和结构上不同的区域，腹侧区域被划分为20个或更多与特定功能系统相关的不同细胞群或核。在实验神经解剖学方法的基础上，设计了三个特定的目标来探索这一假说：(1)基于连接和原位杂交相关的mRNA表达的系统的LHA分化的计算机图形学图谱/数据库。(2)确定和比较背侧和腹侧细胞群的投射。(3)用轴突运输/杂交组织化学相结合的方法确定这些区域的神经细胞类型(表型)。这种分析/综合的方法旨在为功能实验的合理设计提供一个结构框架，并为疾病提供新的见解，并最终对疾病进行治疗，这些疾病涉及前脑神经系统控制、饮食、攻击和防御繁殖、睡眠-觉醒周期，以及可能还有情绪障碍。

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.