CIRCUITRY CONTROLLING THE HIPPOCAMPAL THETA RHYTHM

描述（改编自申请人摘要）：在以前的研究中，我们 证明脑桥口核（RPO）和中缝核 核（MR）直接参与同步（θ）， 分别对海马EEG进行去极化，并且进一步地， 乳头体上核（SUM）是脑干和脑干之间的关键中继， 隔海马在θ节律的控制。 拟议的研究 分为两部分：有合作者和没有合作者的。 非合作研究和非合作研究的主要目的 研究是：（1）检查SUM是否发挥间接（通过 隔膜）和/或直接影响海马体的产生。 θ通过分析对海马EEG的影响， 鹅膏蕈氨酸或胆碱能神经毒素，192 IgG皂草素进入中膜 隔膜对角带;（2）表征几个 脑干/间脑髓核参与控制 海马同步化（脚桥被盖核，核 连合核、乳头体、下丘脑后核和SUM）， 通过检查以下连接进行去髓鞘化（外侧缰核和MR）： 这些核、它们对药理学试剂的反应以及它们的神经元 麻醉和自由活动大鼠的放电特性。 协同 研究：这些研究将与Angel Alonso博士合作完成 （切片电生理学），Csaba Leranth博士（电子显微镜）和 博士马修湖夏皮罗（行为）。 合作的主要目的 主要研究内容有：1）检测大鼠脑电生理特性和反应 对SUM、MB和MS/DBv神经元的各种递质的影响 切片; 2）检查脑干传入神经的突触组织， 的SUM和脑干间脑传入MS/DBv在 超微结构水平; 3）检查鹅膏蕈氨酸和 192 IgG皂草素诱导MS/DBv对记忆的损害，相关变化 与学习和记忆的变化有关。 目前，候选人是 对非研究相关活动承担了很大的义务（即，教学 服务）。 他正在寻求一个KO 2奖，以投入更多的时间进行研究， 发展几个新的研究方向 多份报告显示， 长时程增强（一种记忆的候选机制）最好是 在海马体中通过θ频率的刺激诱导， 有人提出，θ在记忆过程中起着关键作用， 海马体。 如果θ被证明对记忆至关重要， 完全理解负责其产生的神经机制。 这 这项研究可能对阿尔茨海默氏症等疾病有重要意义， 涉及MS/DBv的胆碱能神经元的损失。

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.