Neurovascular Coupling in Cerebrum and Cerebellum

描述（由申请人提供）：功能磁共振成像（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fMRI中绘制的神经血管参数与潜在的神经活动之间的详细关系，目前尚不清楚。在我们之前的工作中，我们证明了血红蛋白浓度和氧合之间的非线性关系，以及大鼠体感觉（桶）皮层的神经元尖峰和突触电活动。在这一建议中，我们将把我们的研究扩展到小脑皮层，以研究是否相同的一般规则可以应用于两种结构的神经血管耦合。虽然本提案的主要重点是小脑，但我们将并行地继续和扩展我们之前在桶状皮层的工作，以促进两者之间的比较(2)。我们将同时进行血液动力学信号（血流、体积、氧合）的光学测量和神经元活动的电生理测量，并将使用经验发展的关系来构建神经血管耦合的“传递函数”。尽管大脑和小脑皮层之间的神经元和血管组织存在根本差异，但考虑到浦肯野细胞和颗粒细胞的总活性，以及区分简单和复杂尖峰的贡献，我们假设耦合的主要原则是守恒的。光学成像技术与“金标准”电生理学的结合不仅为血流动力学和神经元信号的相关性提供了工具，而且可以更好地对大脑活动进行时空估计。因此，除了解决神经血管耦合的问题外，我们将围绕平行纤维对小脑皮层激活的空间延伸的影响来研究小脑生理学的关键问题。这里提出的研究将提供必要的信息，以弥合日益增长的fMRI数据和几代详细的大脑和小脑电生理研究之间的差距。最终，从神经元活动角度准确解读成像数据将在人类疾病的早期发现、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.