Vestibular Influences on Head Direction Cell Activity

描述(申请人提供)：头部方向细胞(HDC)位于大脑的几个区域，包括丘脑的前背核、下丘后核和乳头体外侧核，为确定定向方向提供神经底物。尽管HDC的活动受到各种感觉信号和内部产生的线索的影响，但损伤研究和一些解剖学和生理学证据表明，前庭输入对于维持这些细胞的方向敏感性至关重要。此外，已经提出了相对直接的通路，可以将前庭信号传递到含有HDC的大脑区域。然而，前庭输入必须有相当大的转换，以信号头部的方向，并不确定是否简单的电路，已被认为是中介前庭对HDC的影响，是否能完成这种信号的转换。这项拟议的研究的目的之一是确定是否有一条相对直接的通路将前庭核团与含有HDC的大脑区域联系起来。特异性目的1验证了将逆行跨神经元示踪伪狂犬病病毒注射到HDC的两个区域，即丘脑前背核和乳头体外侧核，导致前庭核神经元在短时间内被标记的假说，表明只有少数突触将HDC与前庭核神经元分开。此外，还没有进行明确的生理学研究，以确定HDC在激活迷路受体的主动头部旋转和动物身体被动旋转过程中是否有类似的反应。如果迷路信号对HDC的方向敏感性有很大的贡献，正如先前的损伤研究所表明的那样，那么这些细胞应该对高频被动水平旋转做出反应，这种旋转有力地激活了半规管传入。特定目的2测试了HDC对水平面上的主动头部旋转和使用转盘施加的被动旋转具有类似反应的假说，包括在黑暗中进行的旋转，从而可获得的主要感觉信息来自迷宫。这些实验将确定前庭系统是否在决定定向航向方面发挥直接和强大的作用，并应该促进对导航神经基础的理解。这项工作还可能为了解外周和中央前庭病变对人类空间认知的潜在影响提供见解。

DESCRIPTION (provided by applicant): Head direction cells (HDC) located in several regions of the brain, including the anterior dorsal nucleus of the thalamus, postsubiculum, and lateral mammillary nuclei, provide the neural substrate for the determination of directional heading. Although activity of HDC is influenced by various sensory signals and internally generated cues, lesion studies and some anatomical and physiological evidence suggest that vestibular inputs are critical for the maintenance of directional sensitivity of these cells. In addition, relatively direct pathways have been proposed that could relay vestibular signals to brain areas containing HDC. However, vestibular inputs must be transformed considerably in order to signal head direction, and it is uncertain whether the simple circuitry that has been postulated to mediate vestibular influences on HDC can accomplish this transformation of signals. One purpose of the proposed research is to establish whether a relatively direct pathway links the vestibular nuclei with brain areas containing HDC. Specific Aim 1 tests the hypothesis that injection of the retrograde transneuronal tracer pseudorabies virus into two areas containing HDC, the anterior dorsal nucleus of the thalamus and lateral mammillary nuclei, results in labeling of neurons in the vestibular nuclei within short survival times, suggesting that only a few synapses separate HDC from vestibular nucleus neurons. Furthermore, definitive physiological studies have not been conducted to determine whether HDC respond similarly during active head rotations and passive rotations of the animal's body that activate labyrinthine receptors. If labyrinthine signals contribute to the directional sensitivity of HDC as substantially as suggested by prior lesion studies, then these cells should respond to high-frequency passive horizontal rotations that powerfully activate semicircular canal afferents. Specific Aim 2 tests the hypothesis that HDC have similar responses to active head rotations in the horizontal plane and passive rotations imposed using a turntable, including rotations delivered in the dark such that the predominant sensory information available is from the labyrinth. These experiments will establish whether the vestibular system plays a direct and powerful role in determining directional heading, and should advance understanding of the neural underpinnings of navigation. This work may also provide insights into potential effects of peripheral and central vestibular lesions on spatial cognition in humans.