Neurovascular Coupling in Cerebrum and Cerebellum

描述(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持有的观看人脑活动的梦想。然而，功能磁共振成像中定位的神经血管参数与潜在神经活动之间的详细关系目前还知之甚少。在我们以前的工作中，我们在大鼠躯体感觉(Barrel)皮质中证明了血红蛋白浓度和氧合作用以及神经元尖峰和突触电活动之间的非线性关系。在这项建议中，我们将把我们的研究扩展到小脑皮质，以调查是否同样的一般规则可以应用于两个结构中的神经血管耦合。虽然这项提案的主要焦点是小脑，但我们将同时继续和扩展我们先前在桶形皮质的工作，以便于两者之间的比较(2)。我们将同时进行血流动力学信号的光学测量(血流、容量、氧合)和神经活动的电生理测量，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”。尽管大脑和小脑皮质在神经元和血管组织方面存在根本差异，但当考虑浦肯野和颗粒细胞的总和活动并区分简单和复杂棘波的贡献时，我们假设耦合的主要原理是守恒的。光学成像技术和“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关联提供了一种工具，而且还使更好的时空估计大脑活动成为可能。因此，除了解决神经血管偶联的问题外，我们还将围绕平行纤维对小脑皮质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，以弥合不断增长的功能磁共振数据与大脑和小脑几代详细的电生理研究之间的差距。最终，从神经元活动的角度准确解释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.