Brainstem-Diencephalic Modulation of the Hippocampus

描述(申请人提供)：我们先前已经证明，口脑桥核(RPO)和中缝正中核分别直接参与海马脑电的同步(theta节律)和去同步，并且乳头上核在RPO和隔区/海马区之间起着控制theta节律的关键中继器的作用。在最近的工作中，我们已经证明在“Papez‘s环路”的几个结构中的细胞有节律性地与theta放电，包括乳头体、Gudden被盖腹侧核和丘脑前腹侧核。这表明，theta节律信号可能在整个Papez环路中共振，可能参与了该环路的助记功能。 拟议的研究将涉及三个主要领域：上升的theta同步系统、上升的海马去同步系统和来自海马区的theta输出系统。Theta同步化结构包括乳头上核和丘脑联合核，去同步化结构包括中缝正中核，Theta输出结构包括丘脑前腹核、悬垂前核和脾后皮质。我们将：(1)使用细胞旁标记技术描述细胞的神经化学标识及其生理特征；(2)检测麻醉和自由活动大鼠的细胞相对于海马脑电的活动；(3)检测细胞的解剖投射，包括光和电子显微镜水平上的递质特异性投射；以及(4)使用2-DG技术检测连续theta后整个大脑中葡萄糖利用的总体模式。通过这一系列的研究，我们打算全面描述参与theta产生的系统以及那些阻止theta在海马区表达的系统(海马脑电去同步化)，并确定海马区对海马区外结构的theta介导的作用，主要是边缘系统和Papez‘s回路的那些结构。 越来越多的证据，包括最近几份显示人类任务相关的theta活动的报告，表明theta节奏在记忆中起着关键作用。如上所述，如果theta被证明对记忆至关重要，我们认为，充分了解theta产生的神经机制以及它对大脑其他区域的作用是至关重要的。这项工作可能对包括科萨科夫综合症、间脑性健忘症和阿尔茨海默病在内的记忆障碍具有重要意义。

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.