An integrative study of neural coding in the vestibular cerebellum: from cellular physiology to models of network behaviour

我们用我们的主要感官--视觉、听觉、嗅觉、味觉和触觉--来表现我们周围的环境。为了处理这些庞大的信息，大脑进化出了专门负责特定类型感觉模式的专门区域。在包括人类在内的哺乳动物中，我们知道当这些信息到达大脑时，它通过这些不同区域内部和之间的多模式整合被置于背景中。例如，我们计算听觉或视觉刺激相对于头部位置的位置的能力，突显了这种整合的成功。前庭信息，即所谓的“第六感”，对整个中枢神经系统的影响可能是最戏剧性的，但却被低估了，它对视觉、听力、运动、认知、睡眠、消化甚至学习和记忆等功能都有贡献。更具体地说，它被认为是人类内部重力模型的基础，也是内在空间坐标系的基础。前庭系统的缺陷会导致空间知觉和记忆受损，以及无法感知自我运动。事实上，到60岁时，失衡会影响到几乎一半的人口，并且与高血压和心绞痛一样普遍。最近的临床研究报道，人类孤立的皮质损伤可导致反复发作的眩晕和失衡，这与灵长类动物和猫的细胞外电生理研究显示前庭对皮质活动的贡献是一致的。在这个项目中，我们将阐明小脑前庭表征的神经机制--已知参与维持平衡、姿势和运动控制的初级结构。我们将结合脑切片中的细胞研究，使我们能够检查涉及调节单细胞兴奋性的微观机制，以及在完好的动物中使用自然刺激的系统方法。计算机模拟将使我们能够在已知的小脑操作的大范围内探索前庭信号的机制。这一发现有助于理解平衡和运动的神经基础，并有助于阐明不平衡和眩晕的根本原因。

We form representations of our surroundings using our primary senses: seeing, hearing, smelling, tasting and touching the world around us. To process this vast array of information brains have evolved specialized regions dedicated to specific types of sensory modalities. In mammals including humans we know when this information reaches the brain it is placed in context through multimodal integration within and between these different regions. The success of this kind of integration is highlighted, for example, by our ability to compute the location of an auditory or visual stimulus relative to head position. Vestibular information, the so-called 'sixth sense' has perhaps the most dramatic and yet underappreciated influence throughout the central nervous system, contributing to functions such as vision, hearing, movement, cognition, sleep, digestion and even learning and memory. More specifically it is presumed to underlie an internal gravity model in humans as well as an intrinsic spatial coordinate system. Defects of the vestibular system result in impaired spatial perception and memory as well as failure to perceive self-motion. In fact disequilibrium affects almost half of the population by age 60 and is as prevalent as hypertension and angina. Recent clinical studies have reported that isolated cortical lesions in humans can cause recurrent episodes of vertigo and imbalance that are consistent with extracellular electrophysiological studies in primates and cats showing vestibular contributions to cortical activity. In this project we will elucidate the neural mechanisms of vestibular representation in the cerebellum- the primary structure know to be involved in maintaining balance, posture and the control of movement. We will combine cellular studies in brain slices that allow us to examine the microscopic mechanisms involved in regulating single cell excitability with a systems approach that uses natural stimulation in the intact animal. Computer simulations will allow us to explore the mechanisms of vestibular signaling on the large scale that the cerebellum is known to operate on. Findings from this provide an understanding of the neural basis of balance and movement and shed light on the underlying causes of disequilibrium and vertigo.