Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
J Neurosci. 2013 Feb 13;33(7):3151-63. doi: 10.1523/JNEUROSCI.4424-12.2013.
During behavioral quiescence, the neocortex generates spontaneous slow oscillations, which may consist of up-states and down-states. Up-states are short epochs of persistent activity that resemble the activated neocortex during arousal and cognition. Neural activity in neocortical pathways can trigger up-states, but the variables that control their occurrence are poorly understood. We used thalamocortical slices from adult mice to explore the role of thalamocortical and intracortical synaptic cooperativity (the number of coincident afferents) in driving up-states. Cooperativity was adjusted by varying the intensity of electrical or blue-light stimuli in pathways that express channelrhodopsin-2. We found that optogenetics greatly improves the study of thalamocortical pathways in slices because it produces thalamocortical responses that resemble those observed in vivo. The results indicate that more synaptic cooperativity, caused by either thalamocortical or intracortical fast AMPA-receptor excitation, leads to more robust inhibition of up-states because it drives stronger feedforward inhibition. Conversely, during strong synaptic cooperativity that suppresses up-states, blocking fast excitation, and as a result the feedforward inhibition it drives, unmasks up-states entirely mediated by slow NMDA-receptor excitation. Regardless of the pathway's origin, cooperativity mediated by fast excitation is inversely related to the ability of excitatory synaptic pathways to trigger up-states in neocortex.
在行为静止期，新皮层会产生自发性的缓慢振荡，其可能由上状态和下状态组成。上状态是短暂的持续活动期，类似于觉醒和认知期间被激活的新皮层。新皮层通路中的神经活动可以引发上状态，但控制其发生的变量尚不清楚。我们使用成年小鼠的丘脑皮层切片来探索丘脑皮层和皮层内突触协同作用（同时传入的传入数量）在驱动上状态中的作用。通过改变表达通道视紫红质-2的通路中的电或蓝光刺激强度来调整协同作用。我们发现光遗传学极大地改善了切片中丘脑皮层通路的研究，因为它产生的丘脑皮层反应类似于在体内观察到的反应。结果表明，更多的突触协同作用（无论是由丘脑皮层还是皮层内快速 AMPA 受体兴奋引起的）导致更强的上状态抑制，因为它驱动更强的前馈抑制。相反，在抑制上状态的强烈突触协同作用期间，阻断快速兴奋以及由此驱动的前馈抑制，会完全揭示出完全由缓慢 NMDA 受体兴奋介导的上状态。无论通路的起源如何，由快速兴奋介导的协同作用与兴奋性突触通路在新皮层中引发上状态的能力呈负相关。
