MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA.
Brain Res. 2011 Feb 4;1372:1-12. doi: 10.1016/j.brainres.2010.11.082. Epub 2010 Dec 8.
Fundamental to the interpretation of neurovascular coupling is determining the neuronal activity that accounts for functional hyperemia. Recently, synaptic and not spiking activity has been found to be responsible for the hemodynamic response. Using pharmacological manipulation in rats, we want to further determine whether the cortical synaptic activity generated by the thalamic input or the subsequent synaptic activity related to secondary cortical processing is driving the hemodynamic response. In this study, we topically applied γ-aminobutyric acid (GABA) in the somatosensory cortex and used electrical forepaw stimulation to evoke neural and vascular activity. In a group of 8 animals, using laminar electrophysiology, we verified that topical application of GABA for 20min does not affect layer IV synaptic activity but reduces subsequent activity in the supragranular and infragranular layers. In another group of 8 animals, we simultaneously measured the electrical and vascular responses with scalp electroencephalography (EEG) and diffuse optical imaging (DOI), respectively. We decomposed somatosensory evoked potentials (SEP) into three major components: P1, N1, and P2, where P1 represents the thalamic input activity originating in layer IV and N1 and P2 represent the subsequent cortical transmissions. We verified that GABA infusion in the somatosensory cortex does not significantly reduce the P1 SEP component but strongly reduces the N1 and P2 components. We found that GABA also elicits a large reduction in the hemodynamic responses, which correlate with the reduction in N1 and P2 components. These results suggest that the hemodynamic response is predominantly driven by cortico-cortical interactions and not by the initial thalamocortical activity in layer IV.
神经血管耦合的解释的基础是确定导致功能充血的神经元活动。最近，发现突触活动而不是尖峰活动负责血液动力学反应。通过在大鼠中进行药理学处理，我们希望进一步确定是由丘脑输入产生的皮质突触活动还是与次级皮质处理相关的后续突触活动驱动血液动力学反应。在这项研究中，我们在体感皮层局部应用γ-氨基丁酸（GABA），并使用电前爪刺激来诱发神经和血管活动。在一组 8 只动物中，我们使用层状电生理学验证了 20 分钟的 GABA 局部应用不会影响第四层的突触活动，但会减少随后在颗粒上和颗粒下层的活动。在另一组 8 只动物中，我们分别使用头皮脑电图（EEG）和漫射光学成像（DOI）同时测量电和血管响应。我们将体感诱发电位（SEP）分解为三个主要成分：P1、N1 和 P2，其中 P1 代表源自第四层的丘脑输入活动，N1 和 P2 代表随后的皮质传递。我们验证了在体感皮层中输注 GABA 不会显著降低 P1 SEP 成分，但强烈降低 N1 和 P2 成分。我们发现 GABA 还会引起血液动力学反应的大幅降低，这与 N1 和 P2 成分的降低相关。这些结果表明，血液动力学反应主要由皮质-皮质相互作用驱动，而不是由第四层的初始丘脑皮质活动驱动。
