Nonlinear neurovascular coupling in rat sensory cortex by activation of transcallosal fibers

Nonlinear neurovascular coupling in rat sensory cortex by activation of transcallosal fibers
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DOI:
10.1038/sj.jcbfm.9600372
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发表时间:
2007-03-01
影响因子:
6.3
通讯作者:
Lauritzen, Martin J.
Lauritzen, Martin J.
中科院分区:
医学1区
文献类型:
--
作者:
Hoffmeyer, Henrik W.;Enager, Pia;Lauritzen, Martin J.

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神经功能成像和正常的脑功能依赖于神经活动和脑血流量之间的强耦合,即神经血管耦合。我们检测了大鼠感觉皮质中神经血管的耦合反应,直接刺激了经穹隆通路,这使得可以检查周围刺激技术无法接触到的大脑区域。用激光多普勒血流仪记录脑血流量和电生理记录的局域场电位(LFP),发现CBF反应与LFP波幅之和呈指数关系。血流动力学反应依赖于谷氨酸受体的激活。AMPA受体阻断剂CNQX可显著减弱所有刺激频率下诱发的CBF反应和LFP波幅。相比之下,MK801阻断N-甲基-D-天冬氨酸(NMDA)受体可减弱高频(>7 Hz)而不是低(<7 Hz)刺激频率下的CBF反应,而不影响诱发的LFP幅度。这表明了使用LFP波幅作为突触活动指示器的局限性。神经元型一氧化氮合酶抑制剂7-硝基吲唑和非特异性环氧合酶抑制剂吲哚美辛分别使血流动力学反应减弱50%~61%和48%~61%,但不影响LFP波幅。这些数据表明,AMPA和NMDA受体的活性保持对于刺激啮齿类大脑半球间联系所引起的全部CBF反应是必要的。AMPA受体激活可产生可测量的LFP,而NMDA受体激活则不能。对CBF有重要影响的神经过程缺乏可测量的LFP,这可能解释了将细胞外电流或电压测量转换为血流动力学响应的一些困难。
Functional neuroimaging and normal brain function rely on the robust coupling between neural activity and cerebral blood flow ( CBF), that is neurovascular coupling. We examined neurovascular coupling in rat sensory cortex in response to direct stimulation of transcallosal pathways, which allows examination of brain regions inaccessible to peripheral stimulation techniques. Using laser-Doppler flowmetry to record CBF and electrophysiologic recordings of local field potentials ( LFPs), we show an exponential relation between CBF responses and summed LFP amplitudes. Hemodynamic responses were dependent on glutamate receptor activation. CNQX, an AMPA receptor blocker, strongly attenuated evoked CBF responses and LFP amplitudes at all stimulation frequencies. In comparison, N- methyl D- aspartate ( NMDA) receptor blockade by MK801 attenuated CBF responses at high ( > 7 Hz) but not low ( < 7 Hz) stimulation frequencies, without affecting evoked LFP amplitudes. This shows the limitation of using LFP amplitudes as indicators of synaptic activity. 7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, and indomethacin, a nonspecific cyclooxygenase inhibitor, attenuated the hemodynamic responses by 50% 61% and 48% 61%, respectively, without affecting LFP amplitudes. The data suggest that preserved activity of both AMPA and NMDA receptors is necessary for the full CBF response evoked by stimulation of rodent interhemispheric connections. AMPA receptor activation gives rise to a measurable LFP, but NMDA receptor activation does not. The lack of a measurable LFP from neural processes that contribute importantly to CBF may explain some of the difficulties in transforming extracellular current or voltage measurements to a hemodynamic response.