Dissecting the roles of neuromodulation and neural activity in neurovascular coupling during behavior

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Abstract Changes in neural activity drive changes in local blood flow in the brain. These changes in cerebral hemodynamics are important for maintaining normal brain health, and are used for non-invasively inferring neural activity. However, hemodynamic signals can decouple from local neural activity, making the understanding of the mechanism of this decoupling critical for interpreting and decoding hemodynamic signals. We hypothesize that hemodynamic signals in a given brain area are controlled by both vasodilatory signals released by local neurons, and by vasoconstrictory neuromodulation, specifically noradrenaline, both of which will vary with behavioral state, such locomotion. We will mechanistically test this hypothesis using optical imaging (intrinsic optical signal imaging and 2-photon microscopy), local pharmacological infusions, chemogenetics, oxygen polarography, and electrophysiology in awake mice. These experiments will elucidate how noradrenergic modulation, which is involved in alertness and attention, interacts with local neural activity to generate changes in blood flow and oxygenation. The end result of these experiments will be a unified understanding of how neural activity and neuromodulation control hemodynamic signals during behavior. 1