PROJECT SUMMARY/ABSTRACT High-resolution functional magnetic resonance imaging (fMRI) is an essential tool to non-invasively study human brain function. To fully utilize high-resolution fMRI application, it is crucial to establish the detailed cellular and signaling pathways for neurovascular coupling. Although our understanding of the signaling pathways has been significantly improved over the last few years, the pathways responsible for producing fMRI signal changes have not been fully clarified yet. The objective in this particular application is to determine the roles of astrocytes, a strong candidate as a neurovascular mediator, to high-resolution fMRI signal evoked by excitatory and inhibitory neuronal activity. To attain this objective, we will apply well-established multimodal techniques, including electrophysiology and fMRI, to the in vivo olfactory bulb model. The olfactory bulb is ideal to address neurovascular coupling issues since each bulb layer contains distinctive neuronal types and specific synapses, and individual layers can be preferentially activated unlike other brain regions. Our results are expected to contribute to the neural-specific interpretation of fMRI maps by revealing the roles of astrocytes in excitatory and inhibitory neuronal activity in sensory stimulation-evoked fMRI responses. Such findings should also provide insight into how neurovascular coupling is impaired in pathological conditions. Since astrocyte functions are impaired in certain diseases, defects in blood flow control may be caused by abnormal astrocyte function rather than from malfunction in neurons and vessels.

PROJECT NARRATIVE The proposed research is relevant to public health because the establishment of the underlying physiological mechanisms of the functional MRI signal is expected to advance the diagnosis and treatment planning of diseases that are associated with disorders like stroke, hypertension, and Alzheimer's disease.