The Integration of Feedforward Locomotor Commands and Sensory Feedback Signals by Medullary Reticulospinal Neurons that Mediate Postural Responses

 描述（由申请人提供）：跌倒相关伤害是一个重大的公共卫生问题。虽然跌倒的病因很复杂，而且因人而异，但人们普遍认为，姿势控制不良的人是跌倒的主要原因， 跌倒风险，经常有感觉功能的缺陷。维持稳定的姿势是一个内在的多感觉过程，需要整合视觉、前庭和躯体输入 从四肢上。本体感觉的重要性在其丧失后突出，这导致姿势不稳定和跌倒。为了在运动过程中保持稳定的平衡， 中枢神经系统可能将前庭和腿部本体感受传入信号与运动命令整合，使得对脊髓中间神经元的下行运动命令在头部在空间中的位置和肢体的机械状态的背景下成形。然而，几乎没有人知道肢体运动和头部运动之间的相互作用，或者这些传入信号和运动命令是否整合在脑干中。这是令人惊讶的，因为来自肢体的信息对于维持平衡至关重要，并且肢体充当响应姿势改变的致动器。中央网状通路独特地定位为肢体、运动和肌肉信号的整合者，然后将整合的信号分配给姿势肌，这是由于 其固有的功能连接性。本申请的主要目标是确定肢体输入对网状脊髓神经元活动的性质，并确定肢体传入信号是否与前庭传入信号和网状脊髓神经元水平的运动命令相结合。提出了两个具体目标。在第一个具体的目标，我们将表征负责传递肢体运动信息的原则感觉传入接受前庭输入的桥脑延髓网状结构神经元。在第二个具体的目标，我们将建立是否网状脊髓神经元整合前庭，前馈运动命令，和肢体反馈信号。这些实验预计将促进对中央网状通路中肢体、胸腺和运动输入的处理的理解，并可能最终为患有运动和平衡障碍的患者带来新的治疗方法。

 DESCRIPTION (provided by applicant): Fall-related injuries represent a significant public health problem. While the etiology of falling is complex and varies considerably from person to person, it is widely recognized that individuals with poor postural control, a major contributor to fall risk, frequently have deficits in sensory function. The maintenance of stable posture is an inherently multisensory process requiring the integration of visual, vestibular, and somatic inputs from the limb. The importance of the proprioceptive senses is highlighted following its loss, which results in postural instability and falling. To achieve stable balance during movement, it is likely that the central nervous system integrates vestibular and leg proprioceptive afferent signals with locomotor commands so that the descending locomotor command to the spinal interneurons is shaped in the context of head position in space and the mechanical state of the limb. However, virtually nothing is known about the interaction between limb movement and head motion, or if these afferent signals and locomotor commands are integrated within the brainstem. This is surprising since information from the limbs is critical to the maintenance of balance, and the limbs serve as the actuators for responding to postural alterations. Central reticular pathways are uniquely positioned to serve as integrators of limb, locomotor, and labyrinthine signals, and then to distribute that integrated signal to the postural muscles, due to their inherent functional connectivity. The primary goals of this application are to determine the nature of the limb input on the activity of reticulospinal neurons and to determine if limb afferen signals are integrated with vestibular afferent signals and locomotor commands at the level of the reticulospinal neuron. Two specific aims are proposed. In the first specific aim, we will characterize the principle sensory afferents responsible for transmitting limb movement information to pontomedullary reticular formation neurons receiving vestibular input. In the second specific aim, we will establish whether reticulospinal neurons integrate vestibular, feedforward locomotor commands, and limb feedback signals. These experiments are expected to advance understanding regarding the processing of limb, labyrinthine, and locomotor inputs in central reticular pathways and may ultimately lead to novel therapies for patients suffering from disorders of locomotion and balance.