Project Summary/Abstract Functional magnetic resonance imaging (fMRI) is a popular method for neuroscience research in humans. This imaging tool relies on hemodynamic responses, such as changes in cerebral blood flow, cerebral blood volume, and blood oxygenation level dependent (BOLD) signals resulting from neuronal activity in the brain. Thus, understanding the relationship between neuronal activity and the resultant hemodynamic responses (i.e., neurovascular coupling) remains a vital area of research for the proper neural interpretation of fMRI maps. It is generally believed that activity of excitatory output neurons, such as cortical pyramidal neurons, is the most faithful indicator of fMRI signal changes because there is good agreement between these sensory- evoked responses in the context of no task demand (e.g., passive exposure to stimuli). However, this assumption may not be valid in the context of demanding cognitive tasks that are often performed during human fMRI experiments. In this context, other neuromodulatory signals, which can evoke hemodynamic responses, seem to play active roles in cognitive processing and sensory information is likely more dependent on behavioral and perceptual needs. Therefore, it is imperative to establish concurrent recordings of neural and fMRI signals in behaving animals to understand neurovascular coupling during context-dependent sensory processing. Our long-term goal is to elucidate the mechanism of context-dependent neurovascular coupling and understand the neural underpinning of fMRI signals, as is most pertinent to human fMRI studies. To attain this goal, the overall objective of this application is to determine the relationship between odor- evoked neuronal activities and fMRI responses in the mouse olfactory bulb and piriform cortex when mice are engaged in olfaction-based behavioral tasks by using concurrent fiber-photometry calcium imaging and fMRI. Our central hypothesis is that sensory-evoked fMRI responses dissociate from activities of excitatory output neurons during context-dependent sensory processing. The rationale for this project is to understand neurovascular coupling in conditions that pertain to human fMRI with cognitive tasks; namely, neurovascular coupling in purposeful behaviors. The research proposed in this application is innovative because the study of neurovascular coupling during context-dependent sensory processing is virtually lacking due to technical challenges in awake animal fMRI with concurrent neural recordings. At the completion of this project, our expected outcomes are to identify how behavioral contexts change the dependency of fMRI responses on excitatory neuronal activities in the olfactory bulb and piriform cortex of behaving mice. Thus, the proposed research is significant in that it provides a direct and firm assessment of the neural substrates of sensory- evoked fMRI responses in a behavioral context, which departs from the status quo of other neurovascular s...