Lecrux Clotilde, Sandoe Claire H, Neupane Sujaya, Kropf Pascal, Toussay Xavier, Tong Xin-Kang, Lacalle-Aurioles María, Shmuel Amir, Hamel Edith
Laboratory of Cerebrovascular Research and
Laboratory of Brain Imaging Signals, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada H3A 2B4.
J Neurosci. 2017 Feb 8;37(6):1518-1531. doi: 10.1523/JNEUROSCI.1784-16.2016. Epub 2017 Jan 9.
Brain imaging techniques that use vascular signals to map changes in neuronal activity rely on the coupling between electrophysiology and hemodynamics, a phenomenon referred to as "neurovascular coupling" (NVC). It is unknown whether this relationship remains reliable under altered brain states associated with acetylcholine (ACh) levels, such as attention and arousal and in pathological conditions such as Alzheimer's disease. We therefore assessed the effects of varying ACh tone on whisker-evoked NVC responses in rat barrel cortex, measured by cerebral blood flow (CBF) and neurophysiological recordings (local field potentials, LFPs). We found that acutely enhanced ACh tone significantly potentiated whisker-evoked CBF responses through muscarinic ACh receptors and concurrently facilitated neuronal responses, as illustrated by increases in the amplitude and power in high frequencies of the evoked LFPs. However, the cellular identity of the activated neuronal network within the responsive barrel was unchanged, as characterized by c-Fos upregulation in pyramidal cells and GABA interneurons coexpressing vasoactive intestinal polypeptide. In contrast, chronic ACh deprivation hindered whisker-evoked CBF responses and the amplitude and power in most frequency bands of the evoked LFPs and reduced the rostrocaudal extent and area of the activated barrel without altering its identity. Correlations between LFP power and CBF, used to estimate NVC, were enhanced under high ACh tone and disturbed significantly by ACh depletion. We conclude that ACh is not only a facilitator but also a prerequisite for the full expression of sensory-evoked NVC responses, indicating that ACh may alter the fidelity of hemodynamic signals in assessing changes in evoked neuronal activity. Neurovascular coupling, defined as the tight relationship between activated neurons and hemodynamic responses, is a fundamental brain function that underlies hemodynamic-based functional brain imaging techniques. However, the impact of altered brain states on this relationship is largely unknown. We therefore investigated how acetylcholine (ACh), known to drive brain states of attention and arousal and to be deficient in pathologies such as Alzheimer's disease, would alter neurovascular coupling responses to sensory stimulation. Whereas acutely increased ACh enhanced neuronal responses and the resulting hemodynamic signals, chronic loss of cholinergic input resulted in dramatic impairments in both types of sensory-evoked signals. We conclude that ACh is not only a potent modulator but also a requirement for the full expression of sensory-evoked neurovascular coupling responses.
利用血管信号来绘制神经元活动变化的脑成像技术依赖于电生理学和血液动力学之间的耦合，这种现象被称为“神经血管耦合”（NVC）。在与乙酰胆碱（ACh）水平改变相关的脑状态下，如注意力和觉醒状态，以及在诸如阿尔茨海默病等病理状况下，这种关系是否仍然可靠尚不清楚。因此，我们评估了不同ACh水平对大鼠桶状皮层中触须诱发的NVC反应的影响，通过脑血流量（CBF）和神经生理学记录（局部场电位，LFPs）进行测量。我们发现，急性增强的ACh水平通过毒蕈碱型ACh受体显著增强了触须诱发的CBF反应，并同时促进了神经元反应，这表现为诱发LFPs高频段的振幅和功率增加。然而，响应桶状区内激活的神经元网络的细胞特性并未改变，其特征是共表达血管活性肠肽的锥体细胞和GABA中间神经元中c-Fos上调。相反，慢性ACh剥夺阻碍了触须诱发的CBF反应以及诱发LFPs大多数频段的振幅和功率，并减小了激活桶状区的前后范围和面积，而不改变其特性。用于估计NVC的LFP功率与CBF之间的相关性在高ACh水平下增强，而被ACh耗竭显著扰乱。我们得出结论，ACh不仅是感觉诱发的NVC反应充分表达的促进因素，也是其先决条件，这表明ACh可能会改变在评估诱发神经元活动变化时血液动力学信号的保真度。神经血管耦合被定义为激活的神经元与血液动力学反应之间的紧密关系，是基于血液动力学的功能性脑成像技术的一项基本脑功能。然而，脑状态改变对这种关系的影响在很大程度上尚不清楚。因此，我们研究了已知能驱动注意力和觉醒脑状态且在诸如阿尔茨海默病等病理状况下缺乏的乙酰胆碱（ACh）将如何改变对感觉刺激的神经血管耦合反应。虽然急性增加的ACh增强了神经元反应以及由此产生的血液动力学信号，但胆碱能输入的慢性丧失导致两种类型的感觉诱发信号都出现显著损伤。我们得出结论，ACh不仅是一种强效调节剂，也是感觉诱发的神经血管耦合反应充分表达的必要条件。
