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

点击翻译按钮获取中文摘要

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 signalling 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.