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

摘要 神经活动的变化驱动大脑局部血流的变化。这些大脑的变化 血液动力学对于维持正常的大脑健康是重要的，并且用于非侵入性地 推断神经活动然而，血液动力学信号可以与局部神经活动解耦， 理解这种分离的机制对于解释和解码至关重要 血流动力学信号。我们假设，在一个给定的大脑区域的血流动力学信号， 由局部神经元释放的血管舒张信号和血管收缩信号控制。 神经调节，特别是去甲肾上腺素，两者都将随行为状态而变化， 运动我们将使用光学成像（固有光学信号）对这一假设进行机械检验 成像和双光子显微镜），局部药物输注，化学遗传学，氧气 极谱法和电生理学。这些实验将阐明 去甲肾上腺素能调节，参与警觉和注意，与局部神经元相互作用， 活动，以产生血液流动和氧合的变化。这些实验的最终结果将 对神经活动和神经调节如何控制血液动力学信号有统一的认识 在行为上。 1

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