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.
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