Gheres Kyle W, Ãœnsal Hayreddin S, Han Xu, Zhang Qingguang, Turner Kevin L, Zhang Nanyin, Drew Patrick J
bioRxiv. 2023 Feb 18:2023.02.18.529057. doi: 10.1101/2023.02.18.529057.
In the adult sensory cortex, increases in neural activity elicited by sensory stimulation usually drives vasodilation mediated by neurovascular coupling. However, whether neurovascular coupling is the same in neonatal animals as adults is controversial, as both canonical and inverted responses have been observed. We investigated the nature of neurovascular coupling in unanesthetized neonatal mice using optical imaging, electrophysiology, and BOLD fMRI. We find in neonatal (postnatal day 15, P15) mice, sensory stimulation induces a small increase in blood volume/BOLD signal, often followed by a large decrease in blood volume. An examination of arousal state of the mice revealed that neonatal mice were asleep a substantial fraction of the time, and that stimulation caused the animal to awaken. As cortical blood volume is much higher during REM and NREM sleep than the awake state, awakening occludes any sensory-evoked neurovascular coupling. When neonatal mice are stimulated during an awake period, they showed relatively normal (but slowed) neurovascular coupling, showing that that the typically observed constriction is due to arousal state changes. These result show that sleep-related vascular changes dominate over any sensory-evoked changes, and hemodynamic measures need to be considered in the context of arousal state changes.
In the adult brain, increases in neural activity are often followed by vasodilation, allowing activity to be monitored using optical or magnetic resonance imaging. However, in neonates, sensory stimulation can drive vasoconstriction, whose origin was not understood. We used optical and magnetic resonance imaging approaches to investigate hemodynamics in neonatal mice. We found that sensory-induced vasoconstriction occurred when the mice were asleep, as sleep is associated with dilation of the vasculature of the brain relative to the awake state. The stimulus awakens the mice, causing a constriction due to the arousal state change. Our study shows the importance of monitoring arousal state, particularly when investigating subjects that may sleep, and the dominance arousal effects on brain hemodynamics.
在成体感觉皮层中，感觉刺激引发的神经活动增加通常会驱动由神经血管耦合介导的血管舒张。然而，神经血管耦合在新生动物中是否与成体相同存在争议，因为已经观察到了典型反应和反向反应。我们使用光学成像、电生理学和血氧水平依赖性功能磁共振成像（BOLD fMRI）研究了未麻醉新生小鼠的神经血管耦合性质。我们发现在新生（出生后第15天，P15）小鼠中，感觉刺激会导致血容量/血氧水平依赖信号小幅增加，随后通常会出现血容量大幅下降。对小鼠觉醒状态的检查显示，新生小鼠大部分时间处于睡眠状态，且刺激会使动物醒来。由于快速眼动（REM）和非快速眼动（NREM）睡眠期间皮层血容量比清醒状态下高得多，觉醒会阻断任何感觉诱发的神经血管耦合。当新生小鼠在清醒期受到刺激时，它们表现出相对正常（但较慢）的神经血管耦合，表明通常观察到的血管收缩是由于觉醒状态变化所致。这些结果表明，与睡眠相关的血管变化比任何感觉诱发的变化更为显著，并且在考虑觉醒状态变化的背景下需要对血流动力学测量进行考量。
在成体大脑中，神经活动增加通常会伴随血管舒张，从而可以使用光学或磁共振成像来监测活动。然而，在新生儿中，感觉刺激可驱动血管收缩，其起源尚不清楚。我们使用光学和磁共振成像方法研究新生小鼠的血流动力学。我们发现，当小鼠处于睡眠状态时会发生感觉诱发的血管收缩，因为睡眠与相对于清醒状态下大脑血管舒张有关。刺激会使小鼠醒来，由于觉醒状态变化而导致血管收缩。我们的研究表明了监测觉醒状态的重要性，特别是在研究可能睡眠的受试者时，以及觉醒对脑血流动力学的主导作用。
