The relationship between blood flow and neuronal activity in the rodent olfactory bulb
The relationship between blood flow and neuronal activity in the rodent olfactory bulb
复制标题
DOI：
10.1523/jneurosci.3141-06.2007
复制
发表时间：
2007-06-13
影响因子：
5.3
通讯作者：
Charpak, Serge
中科院分区：
文献类型：
--
作者：
Chaigneau, Emmanuelle;Tiret, Pascale;Charpak, Serge
在大脑中，神经元激活会引发脑血流量（CBF）的增加。本文采用两种动物模型和多种技术（脑血流和神经元钙动力学的双光子成像、细胞内和细胞外记录、局部药理学）分析了啮齿动物嗅球在气味刺激过程中神经元活动与局部脑血流的关系。谷氨酸受体拮抗剂或河豚毒素直接应用于单个大鼠嗅觉肾小球阻断突触后反应，但不影响局部气味诱发的CBF增加。这表明，在我们的实验条件下，气味总是激活多个肾小球，而沉默少数聚集肾小球中的一个并不影响血管反应。为了更广泛地阻断突触传递，我们在转基因G-CaMP2小鼠的嗅球表面过量使用谷氨酸拮抗剂。这有两个原因：(1)与大鼠相比，小鼠的嗅觉神经层较薄，这有利于药物进入肾小球层；(2)转基因G-CaMP2小鼠在二尖瓣细胞中表达荧光钙传感器蛋白G-CaMP2。在G-CaMP2小鼠中，气味诱发、气味特异性和浓度依赖性的肾小球钙增加。谷氨酸受体拮抗剂的过量可阻断气味诱发的突触后钙信号和脑血流反应。我们得出结论，突触后谷氨酸受体的激活和树突状钙的增加是嗅球肾小球神经血管耦合的主要步骤。
In the brain, neuronal activation triggers an increase in cerebral blood flow ( CBF). Here, we use two animal models and several techniques ( two-photon imaging of CBF and neuronal calcium dynamics, intracellular and extracellular recordings, local pharmacology) to analyze the relationship between neuronal activity and local CBF during odor stimulation in the rodent olfactory bulb. Application of glutamate receptor antagonists or tetrodotoxin directly into single rat olfactory glomeruli blocked postsynaptic responses but did not affect the local odor-evoked CBF increases. This suggests that in our experimental conditions, odor always activates more than one glomerulus and that silencing one of a few clustered glomeruli does not affect the vascular response. To block synaptic transmission more widely, we then superfused glutamate antagonists over the surface of the olfactory bulb in transgenic G-CaMP2 mice. This was for two reasons: ( 1) mice have a thin olfactory nerve layer compared to rats and this will favor drug access to the glomerular layer, and ( 2) transgenic G-CaMP2 mice express the fluorescent calcium sensor protein G-CaMP2 in mitral cells. In G-CaMP2 mice, odor-evoked, odor-specific, and concentration-dependent calcium increases in glomeruli. Superfusion of glutamate receptor antagonists blocked odor-evoked postsynaptic calcium signals and CBF responses. We conclude that activation of postsynaptic glutamate receptors and rises in dendritic calcium are major steps for neurovascular coupling in olfactory bulb glomeruli.