CIRCUITRY CONTROLLING THE HIPPOCAMPAL THETA RHYTHM

描述(摘自申请者的摘要)：在以前的研究中，我们 结果显示，脑桥口侧核(RPO)和中缝正中核 核(MR)直接参与同步化(Theta)和 海马区脑电的去同步化，并进一步 乳房上核(SUM)是脑干和中枢神经之间的重要中继核。 隔中隔中的海马体控制着theta节律。建议进行的研究 分为两部分：有合作者完成的和没有合作者完成的。 非合作研究与非合作研究的主要目标 研究内容包括：(1)检验总和是否产生间接影响(通过 隔)和/或对海马体的直接影响 Theta分析注射青蒿素对大鼠海马区脑电的影响 鹅膏菌素或胆碱能神经毒素、192球蛋白进入内侧 隔膜斜带；和(2)表征几个 脑干/间脑核团可能参与控制 海马体同步化(桥脑脚被盖核、核 神经元、乳头体、下丘脑后核和SUM)和 去同步化(外侧缰核和MR) 这些核、它们对药物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。协作性 研究：这些研究将与安吉尔·阿隆索博士合作完成 (切片电生理学)，Csaba Leranth博士(电子显微镜)和 马修·L·夏皮罗博士(行为)。协作的主要目标是 研究内容包括：1)检测脑电生理特性和反应 对SUM、MB和MS/DBV神经元不同递质的体外研究 切片；2)观察脑干传入神经元的突触组织 MS/DBV的SUM和脑干间脑传入 超微结构水平；3)观察鹅膏藤酸和牛磺酸的作用。 192 Ig G皂苷诱导的MS/DBV对记忆的损害及其相关性变化 与学习和记忆的变化有关。目前，候选人是 非常有义务从事与研究无关的活动(例如，教学 和服务)。他正在寻求KO2奖，以将更多的时间投入到研究和 来发展几个新的研究方向。多份报告显示， 长时程增强(记忆的一种候选机制)是最佳的 在海马区通过刺激theta频率诱导，它有 提出题元在记忆过程中起着关键作用。 海马体。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影响 涉及MS/DBV胆碱能神经元的丢失。

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.