CIRCUITRY CONTROLLING THE HIPPOCAMPAL THETA RHYTHM

控制海马 Theta 节律的电路

基本信息

批准号：
6538246
负责人：
ROBERT Paul Vertes
金额：
$ 10.91万
依托单位：
FLORIDA ATLANTIC UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-07-01 至 2004-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6538246
关键词：
brain electrical activity brain mapping brain stem cholinergic agents electroencephalography electron microscopy hippocampus hypothalamus ibotenate immunocytochemistry immunoglobulin G injection /infusion laboratory rat light microscopy memory neuropharmacology neurotoxins serotonin

项目摘要

DESCRIPTION (Adapted from applicant's abstract): In previous studies, we demonstrated that the nucleus pontis oralis (RPO) and the median raphe nucleus (MR) are directly involved in the synchronization (theta) and desynchronization of the hippocampal EEG, respectively, and further that the supramammilliary nucleus (SUM) is a critical relay between the brainstem and septum hippocampus in the control of the theta rhythm. The proposed studies are divided into two parts; those done with and without collaborators. Non-collaborative studies and the primary aims of the non-collaborative studies are: (1) to examine whether the SUM exerts an indirect (through the septum) and/or direct influence on the hippocampus in the generation of theta by analyzing the effects on the hippocampal EEG of injections of ibotenic acid or the cholinergic neurotoxin, 192 IgG saporin into the medial septum diagonal band; and (2) to characterize the role of several brainstem/diencephalic nuclei putatively involved in the control of hippocampal synchronization (pedunculopontine tegmental nucleus, nucleus reuniens, mammillary body, posterior nucleus of hypothalamus and SUM) and desynchronization (lateral habenula and MR) by examining the connections of these nuclei, their response to pharmacological agents and their neuronal discharge properties in anesthetized and freely moving rats. Collaborative Studies: These studies will be done in collaboration with Dr. Angel Alonso (electrophysiology in slices), Dr. Csaba Leranth (electron microscopy) and Dr. Matthew L. Shapiro (behavior). The primary aims of the collaborative studies are: 1) to examine the electrophysiological properties and response to various transmitter agents of SUM, MB and MS/DBv neurons in in vitro slices; 2) to examine the synaptic organization of brainstem afferents to the SUM and brainstem diencephalic afferents to the MS/DBv at the ultrastructural level; and 3) to examine the effects of ibotenic acid and 192 IgG saporin induced lesions of the MS/DBv on memory, correlating changes in theta to changes in learning and memory. At present, the candidate is very heavily obligated to non-research related activities (i.e., teaching and service). He is seeking a KO2 award to devote more time to research and to develop several new lines of research. Several reports have shown that long-term potentiation (a candidate mechanism for memory) is optimally induced in the hippocampus by stimulation at the theta frequency, and it has been proposed that theta plays a pivotal role in mnemonic processes in the hippocampus. If theta proves to be critical for memory, it is important to fully understand the neural mechanisms responsible for its generation. This work may have important implications for conditions such as Alzheimer's that involve a loss of cholinergic neurons of the MS/DBv.

描述（改编自申请人的摘要）：在先前的研究中，我们证明了蓬蒂斯核Oralis（RPO）和中位raphe 核（MR）直接参与同步（theta）和海马脑电图分别是对的，进一步的超拟核核（SUM）是脑干和 theta节奏的控制中的隔膜海马。提出的研究分为两个部分；那些与合作者一起完成的。非授权研究和非授权的主要目的研究是：（1）检查总和是否施加间接（通过隔膜）和/或直接影响海马的产生通过分析对注射海马脑电图的影响伊布丁酸或胆碱能神经毒素，192 IgG皂苷进入内侧隔隔对角带；（2）表征几个脑干/双脑核涉及控制的海马同步（Pedunculopontine换罩核，核，核聚会，乳房乳房，下丘脑的后核和总和）和通过检查的连接这些核，它们对药理剂及其神经元的反应麻醉和自由移动的大鼠的排放特性。协作研究：这些研究将与Angel Alonso博士合作完成（切片中的电生理学），Csaba Leranth博士（电子显微镜）和 Matthew L. Shapiro博士（行为）。协作的主要目的研究是：1）检查电生理特性和反应在体外，MB和MS/DBV神经元的各种发射机剂切片； 2）检查脑干传入的突触组织对MS/DBV的总和和脑干双重传入超微结构水平； 3）检查依botenic酸和 192 IgG皂苷在存储器上诱导MS/DBV的病变，将变化相关联在Theta中，学习和记忆的变化。目前，候选人是非常严重地义务与非研究相关的活动（即教学和服务）。他正在寻求KO2奖，以花费更多时间进行研究和开发一些新的研究线。几份报告表明长期增强（一种记忆的候选机制）是最佳的通过在theta频率下刺激在海马中诱导，它具有被提出，theta在助记符过程中起关键作用海马。如果theta被证明对记忆至关重要，那么重要的是充分了解导致其代理的神经机制。这工作可能对诸如阿尔茨海默氏症这样的条件具有重要意义涉及MS/DBV的胆碱能神经元丧失。