Vestibular Influences on Head Direction Cell Activity

描述（由申请人提供）：头部定向细胞（HDC）位于大脑的几个区域，包括丘脑前背核、后枕核和侧乳核，为定向定向的确定提供神经基质。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，但病变研究和一些解剖学和生理学证据表明，前庭输入对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途径，可以将前庭信号传递到含有HDC的大脑区域。然而，前庭输入必须经过相当大的转换，才能发出头部方向的信号，而目前尚不确定的是，被假定为介导前庭对HDC影响的简单电路是否能完成这种信号的转换。提出的研究的目的之一是确定是否有一个相对直接的途径将前庭核与含有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剂伪狂犬病病毒注射到含有HDC的两个区域，即丘脑前背核和外侧乳头核，可在短存活时间内标记前庭核中的神经元，这表明只有少数突触将HDC与前庭核神经元分开。此外，尚无明确的生理学研究来确定HDC在激活迷路受体的主动头部旋转和被动身体旋转时是否有相似的反应。如果迷路信号对HDC的方向敏感性的贡献与之前的病变研究一致，那么这些细胞应该对高频被动水平旋转做出反应，从而有力地激活半圆管传入神经。具体目标2测试假设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有相似的反应，包括在黑暗中传递的旋转，这样主要的感官信息来自迷宫。这些实验将确定前庭系统是否在确定方向方向方面起着直接而有力的作用，并将促进对导航神经基础的理解。这项工作也可能为周围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.