Specific subtypes of cortical GABA interneurons contribute to the neurovascular coupling response to basal forebrain stimulation
Specific subtypes of cortical GABA interneurons contribute to the neurovascular coupling response to basal forebrain stimulation
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DOI：
10.1038/sj.jcbfm.9600558
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发表时间：
2008-02-01
影响因子：
6.3
通讯作者：
Hamel, Edith
中科院分区：
文献类型：
--
作者：
Kocharyan, Ara;Fernandes, Priscilla;Hamel, Edith
神经血管耦合，或神经元活动和局部脑血流量（CBF）之间的紧密耦合，似乎主要是由激活区域内传入信号的局部处理驱动的。为了测试皮质γ-氨基丁酸（GABA）中间神经元-皮质活动的局部整合者-是否参与这种耦合，我们在体内刺激基底皮质通路，监测皮质CBF，并确定激活的中间神经元（c-Fos-免疫阳性）和参与这种反应的神经介质。基底前脑（BF）刺激诱导同侧增加CBF和选择性激活层II至VI生长抑素和/或神经肽Y的含，以及层I GABA中间神经元。一氧化氮合酶中间神经元显示弱的双边激活，而血管活性肠多肽或乙酰胆碱（ACh）含有GABA的中间神经元没有被激活。选择性胆碱能去传入表明，ACh释放刺激BF传入触发CBF反应，但后者介导的，部分，从胆碱能皮层中间神经元的GABA的局部释放，并通过GABA-A受体介导的传输。这些数据表明，激活GABA中间神经元的特定子集和GABA-A介导的对神经元、血管和/或星形胶质细胞靶点的作用对于BF刺激的血流动力学反应的充分表达是必要的。此外，这些发现强调了理解血液动力学信号背后的细胞网络和电路的重要性，因为只有特定的神经元子集才能被给定的刺激激活，这取决于它们接收和整合的传入输入。
Neurovascular coupling, or the tight coupling between neuronal activity and regional cerebral blood flow (CBF), seems largely driven by the local processing of incoming afferent signals within the activated area. To test if cortical gamma-aminobutyric acid (GABA) interneurons - the local integrators of cortical activity - are involved in this coupling, we stimulated the basalocortical pathway in vivo, monitored cortical CBF, and identified the activated interneurons (c-Fos-immunopositive) and the neuromediators involved in this response. Basal forebrain (BF) stimulation induced ipsilateral increases in CBF and selective activation of layers II to VI somatostatin- and/or neuropeptide Y-containing, as well as layer I GABA interneurons. Nitric oxide synthase interneurons displayed weak bilateral activation, whereas vasoactive intestinal polypeptide- or acetylcholine (ACh)-containing GABA interneurons were not activated. Selective cholinergic deafferentation indicated that ACh released from stimulated BF afferents triggered the CBF response, but the latter was mediated, in part, by the local release of GABA from cholinoceptive cortical interneurons, and through GABA-A receptor-mediated transmission. These data show that activation of specific subsets of GABA interneurons and their GABA-A-mediated effects on neuronal, vascular, and/or astroglial targets are necessary for the full expression of the hemodynamic response to BF stimulation. Further, these findings highlight the importance of understanding the cellular networks and circuitry that underlie hemodynamic signals, as only specific subsets of neurons may be activated by a given stimulus, depending on the afferent inputs they receive and integrate.