Impact of Thalamic Impulses On Awake Neocortex

这一建议旨在了解丘脑皮质感觉信息进入新皮质网络并在不同行为状态下进行处理的机制。哺乳动物的背侧丘脑是一个门户，除嗅觉外，所有的感觉信息都必须通过它才能进入感觉新皮质。丘脑核团的单个神经元有两种截然不同的工作模式：“接力”模式和“爆发”模式。中继模式主要发生在警戒状态，突触通过丘脑的传递是非常有效的。相比之下，突发模式主要与注意力不集中、嗜睡和睡眠有关，通过丘脑的突触传输受到抑制。在理解这些丘脑模式的潜在机制及其在知觉中的作用方面，人们付出了相当大的努力，丘脑爆发与注意机制有关。然而，在我们理解丘脑爆裂的知觉后果方面，一个关键的环节仍然没有被探索：我们不知道丘脑在丘脑皮质突触处爆裂冲动的命运。人们可以期待突触效率的降低，就像在猝发模式下发生在视网膜膝状突触上的那样，或者是丘脑突发冲动激活新皮质回路的效率增加。我们的初步工作显示，丘脑皮质爆发对躯体感觉“桶”皮质内一类皮质抑制神经元的突触影响有明显的增强作用。拟议的实验将通过以下方式扩展这些结果：(A)检查在不同行为/脑电状态下研究的丘脑皮质脉冲爆发对兴奋性皮质群体的影响，以及(B)检查丘脑爆发导致的皮层内兴奋的传播。所有实验都将在清醒的受试者中使用新颖的细胞外和细胞内多电极方法进行。将同时研究S1桶内丘脑皮质投射神经元和不同类别的皮质神经元的活动，并将使用互相关法、突触后电位的峰触发平均和电流源密度分析方法来分析这些已识别的神经元之间的相互作用。我们假设，突发性丘脑冲动会产生增强的丘脑皮质和皮质内兴奋传播。这些数据将提供在清醒状态下自然条件下研究的丘脑皮质网络的独特视角。

This proposal is aimed at understanding the mechanisms by which thalamocortical sensory information gains access to neocortical networks and is processed during different behavioral states. The mammalian dorsal thalamus serves as a gateway through which all sensory information, other than olfaction, must pass before gaining access to sensory neocortex. The individual neurons of thalamic nuclei operate in two distinct modes: "relay" mode and "burst" mode. Relay mode occurs primarily in the alert state, and synaptic transmission through the thalamus is highly effective. In contrast, burst mode has been primarily associated with inattention, drowsiness, and sleep, and synaptic transmission through the thalamus is depressed. Considerable effort has gone into understanding the mechanisms underlying these thalamic modes and their role in perception, and thalamic bursts have been linked to mechanisms of attention. However, a crucial link in our understanding of the perceptual consequences of thalamic bursting has remained unexplored: we do not know the fate of bursting thalamic impulses at the thalamocortical synapse. One could expect either a decrease in synaptic efficacy, as occurs at the retino-geniculate synapse during burst mode, or an increase in the efficacy with which bursting thalamic impulses activate neocortical circuits. Our preliminary work has shown a potent enhancement in the synaptic impact of thalamocortical bursts onto a class of cortical inhibitory neuron within somatosensory "barrel" cortex. The proposed experiments will extend these results by (a) examining the effect of bursting thalamocortical impulses on excitatory cortical populations studied during different behavioral/EEG states, and (b) examining the intracortical spread of excitation that results from thalamic bursts. All experiments will be performed in awake subjects using novel extracellular and intracellular multi-electrode methods. The activity of thalamocortical projection neurons and cortical neurons of different classes within S1 barrels will be simultaneously studied, and interactions among these identified neurons will be analyzed using methods of cross-correlation, spike-triggered averaging of post-synaptic potentials, and current source-density analysis. We hypothesize that bursting thalamic impulses generate an enhanced thalamocortical and intracortical spread of excitation. These data will offer a unique view of thalamocortical networks studied under natural conditions in the awake state.