Brainstem-Diencephalic Modulation of the Hippocampus

描述（由申请人提供）：我们之前已经证明，脑桥口核（RPO）和中缝正中核分别直接参与海马EEG的同步化（θ节律）和去同步化，并且上丘脑核在θ节律的控制中充当RPO和隔/海马之间的关键中继。在最近的工作中，我们已经表明，细胞在几个结构的“帕佩兹电路”消防节奏与θ包括乳头体，腹侧被盖核的Gudden和丘脑腹前核。这表明θ节律信号可能在帕佩兹的回路中产生共鸣，可能与回路的记忆功能有关。 这些研究将涉及三个主要领域：上行θ同步系统、上行海马去同步系统和海马θ输出系统。θ同步结构包括丘脑的乳头体上核和连合核;去同步结构包括中缝核，θ输出结构包括丘脑的前腹侧核、前下托和压后皮质。我们将：（1）用神经细胞标记技术描述细胞的神经化学特性及其生理特征;（2）检查麻醉和自由活动大鼠海马EEG的细胞活性;（3）检查细胞的解剖投射，包括光镜和电镜水平上的递质特异性投射;和（4）使用2-DG技术检查连续θ波后整个大脑葡萄糖利用的总体模式。通过这一系列的研究，我们打算充分表征参与theta生成的系统和那些阻断其在海马中表达的系统（海马EEG去极化），以及定义海马对海马外结构（主要是边缘系统和Papez电路）的theta介导的作用。 越来越多的证据，包括最近几份显示人类与任务相关的θ活动的报告，表明θ节律在记忆中起着关键作用。如果如前所述，theta被证明对记忆至关重要，我们相信完全理解产生theta的神经机制及其对大脑其他区域的作用至关重要。这项工作可能对记忆障碍，包括科尔萨科夫综合征，间脑性遗忘症和阿尔茨海默病有重要的意义。

DESCRIPTION (provided by applicant): We have previously demonstrated that the nucleus pontis oralis (RPO) and the median raphe nucleus are directly involved in the synchronization (theta rhythm) and desynchronization of the hippocampal EEG, respectively, and that the suprammillary nucleus serves as a critical relay between RPO and the septum/hippocampus in the control of the theta rhythm. In recent work, we have shown that cells in several structures of "Papez's circuit" fire rhythmically with theta including the mammillary bodies, the ventral tegmental nucleus of Gudden and the anterior ventral nucleus of the thalamus. This suggests that a theta rhythmic signal may resonate throughout Papez's circuit, possibly involved in mnemonic functions of the circuit. The proposed studies will involve three main areas: ascending theta synchronizing systems, ascending hippocampal desynchronizing systems and theta output systems from the hippocampus. Theta synchronizing structures include the supramammillary nucleus and nucleus reuniens of the thalamus; desynchronizing structures include the median raphe nucleus, and theta output structures include the anterior ventral nucleus of thalamus, the presubiculum and the retrosplenial cortex. We will: (1) describe the neurochemical identity of cells together with their physiological profiles using juxtacellular labeling techniques; (2) examine the activity of cells in anesthetized and freely moving rats with respect to the hippocampal EEG; (3) examine the anatomical projections of cells including transmitter specific projections at the light and electron microscopic level; and (4) examine overall patterns of glucose utilization throughout the brain following continuous theta using the 2-DG technique. With this series of studies, we intend to fully characterize systems involved in the generation of theta and those that block its expression in the hippocampus (hippocampal EEG desynchronization) as well as define theta-mediated actions of the hippocampus on extra-hippocampal structures, primarily those of the limbic system and Papez's circuit. An accumulating body of evidence, including several recent reports showing task related theta activity in humans, indicates that the theta rhythm serves a critical role in memory. If, as indicated, theta proves to be critical for memory, we believe it is vitally important to fully understand the neural mechanisms responsible for the generation of theta as well as its actions on other regions of the brain. This work may have important implications for disorders of memory including Korsakoff's syndrome, diencephalic amnesia and Alzheimer's disease.