The Physiological Mechanisms and Role in Neural Coding of Functional Hyperemia

项目总结 大脑中神经元的激活导致局部血流量增加--这一现象被称为 功能性充血。广泛使用的血流动力学成像技术，如功能磁共振成像，利用 功能性充血从血管反应中推断神经活动。然而，血管系统似乎 对神经元活动的反应过度补偿--血流量在一个更大的区域内增加 活跃的神经组织，血液的增加似乎超过了组织的氧气需求。因此，a 更深入地了解血流变化反映神经活动的程度对于 准确解释血流动力学成像数据。此外，尽管它被认为是功能性的 充血是分配有限资源的一种有效手段，令人惊讶的是，我们对它的重要性知之甚少 这种血流量的增加是为了神经组织的健康和功能。这项提案的首要目标是 是为了了解血液供应过剩在功能性疾病中的机制和作用 充血。我们最近发现，皮质实质中的个别血管表现为刺激诱发 即使血管周围的组织对刺激没有反应，血流量也会增加。在目标1中，我们将 检测神经组织活跃区域外的血流量增加是否由远程照射引起 动脉扩张信号通过软膜网的传播。动脉扩张已经被证明可以传播 通过血管壁内皮细胞的长距离传播。我们将修改一种技术来破坏这一点 使用双光子显微镜进行传播，并确定阻断血管扩张的传播是否会导致 神经和血管活动的位置之间更精确的对应。在目标2中，我们将开发 在体光控单个小动脉直径研究功能性血管病变的技术 充血对神经反应的影响。使用双光子光遗传学，我们将防止血液流入 被感官刺激激活的组织区域。我们将分析波幅和波幅 神经元放电和突触反应的刺激选择性因缺乏额外血液而受到影响。这些 结果将帮助我们理解正常的神经元功能是如何依赖于强大的神经血管耦合的。这 进而将阐明在许多疾病中出现的神经血管耦合缺陷是否是导致 伴随而来的神经紊乱。这项建议将有助于建立技术和模型系统 未来的研究旨在了解神经活动如何导致局部血流，并进而依赖于局部血流。 改变。

PROJECT SUMMARY The activation of neurons in the brain leads to localized blood flow increases – a phenomenon termed functional hyperemia. Widely used hemodynamic imaging techniques, such as fMRI, take advantage of functional hyperemia to infer neural activity from vascular responses. However, the vasculature seems to overcompensate in its reaction to neuronal activity – blood flow increases over a larger region than the area of active neural tissue, and the increase in blood seems to exceed the oxygen needs of the tissue. Therefore, a deeper understanding of the degree to which blood flow changes reflect neural activity is critical for the accurate interpretation of hemodynamic imaging data. Additionally, although it is supposed that functional hyperemia is an efficient means of distributing limited resources, we know surprisingly little about how critical this blood flow increase is for the health and function of neural tissue. The overarching goal of this proposal is to understand the mechanisms and the functional role of the overshoot of blood supply in functional hyperemia. We recently found that individual vessels in the cortical parenchyma display stimulus-evoked blood flow increases even when the tissue around the vessel was unresponsive to the stimuli. In Aim 1, we will test if the increase in blood flow seen outside of the region of active neural tissue is caused by long-range propagation of arterial dilation signals through the pial network. Arterial dilation has been shown to propagate over long distances through endothelial cells in the vessel walls. We will modify a technique for disrupting this propagation using two-photon microscopy and determine if interrupting the propagation of vasodilation leads to a more precise correspondence between the locations of neural and vascular activity. In Aim 2, we will develop a technique for optically controlling the diameter of individual arterioles in vivo to study the effect of functional hyperemia on neural responses. Using two-photon optogenetics, we will prevent increased blood flow into regions of tissue which have been activated by sensory stimuli. We will analyze how the amplitude and stimulus selectivity of neuronal spiking and synaptic responses are affected by the lack of extra blood. These results will help us understand how normal neuronal function depends on robust neurovascular coupling. This in turn will shed light on whether the neurovascular coupling defects seen in many diseases are the cause of the accompanying neurological disorders. This proposal will help establish techniques and model systems for future studies aimed at understanding how neural activity leads to, and in turn depends on, local blood flow changes.