Neurovascular Coupling in Cerebrum and Cerebellum

描述（由申请人提供）：功能性磁共振成像（fMRI）有可能实现神经科学界和广大公众长期以来的梦想，即观察人类大脑的活动。然而，在功能磁共振成像映射的神经血管参数之间的详细关系，和潜在的神经活动，目前知之甚少。在我们以前的工作中，我们证明了血红蛋白浓度和氧合之间的非线性关系，神经元尖峰和突触电活动在大鼠躯体感觉（桶）皮层。在这个建议中，我们将我们的研究扩展到小脑皮质，以调查是否相同的一般规则可以适用于神经血管耦合在这两个结构。虽然这个建议的主要焦点是小脑，但我们将同时继续并扩展我们以前在桶状皮层的工作，以促进两者之间的比较（2）。我们将同时进行血流动力学信号（血流量，体积，氧合）和神经元活动的电生理测量的光学测量，并将使用经验开发的关系，以构建一个“传递函数”的神经血管耦合。尽管大脑和小脑皮质之间的神经元和血管组织的根本差异，我们假设一个保守的耦合的主要原则时，考虑到浦肯野细胞和颗粒细胞的总和活动，并区分简单和复杂的尖峰的贡献。光学成像技术和“金标准”电生理学的组合不仅提供了一种工具，用于相关的血液动力学和神经元信号，而且还能够更好地时空估计大脑活动。因此，除了解决神经血管耦合的问题，我们将研究小脑生理学的关键问题，围绕平行纤维对小脑皮层激活的空间延伸的影响。本文的研究将为填补大脑和小脑功能磁共振成像数据与电生理研究之间的差距提供重要信息。最终，准确解释神经元活动方面的成像数据将在人类疾病的早期检测、诊断和治疗中发挥重要作用。

DESCRIPTION (provided by applicant): Functional Magnetic Resonance Imaging (fMRI) has the potential of fulfilling a long held dream of the neuroscience community and of the public at large to view the human brain in action. However, the detailed relation between the neurovascular parameters mapped in fMRI, and the underlying neural activity, are poorly understood at present. In our previous work we demonstrated a nonlinear relationship between hemoglobin concentration and oxygenation, and neuronal spiking and synaptic electrical activity in rat somatosensory (Barrel) cortex. In this proposal we will extend our study to the cerebellar cortex in order to investigate whether the same general rules can be applied to neurovascular coupling in both structures. While the main focus of this proposal is on the cerebellum, we will in parallel continue and expand our previous work in Barrel cortex to facilitate the comparison between the two (2). We will perform simultaneous optical measurements of hemodynamic signals (blood flow, volume, oxygenation) and electrophysiological measurements of neuronal activity, and will use an empirically developed relationship to construct a "transfer function" of neurovascular coupling. Despite fundamental differences in neuronal and vascular organization between cerebral and cerebellar cortices we hypothesize a conservation of the main principles of coupling when taking into account the sum activity of Purkinje and granule cells, and differentiating the contribution of simple and complex spikes. The combination of optical imaging techniques and "gold standard" electrophysiology not only provides a tool for correlation of hemodynamic and neuronal signals, but also enables better spatio-temporal estimation of brain activity. Thus, in addition to addressing the question of neurovascular coupling, we will study key questions of cerebellar physiology centered around the influence of parallel fibers on spatial extend of cerebellar cortical activation. Investigations proposed here will provide essential information to bridge the gap between the growing body of fMRI data and generations of detailed electrophysiological studies in cerebrum and cerebellum. Ultimately, accurate interpretation of imaging data in terms of neuronal activity will play an important role in the early detection, diagnosis and treatment of human disease.