Impact of Thalamic Impulses On Awake Neocortex

该建议旨在了解丘脑皮层感觉信息进入新皮层网络并在不同行为状态下处理的机制。 哺乳动物的背侧丘脑是一个通道，除了嗅觉之外，所有的感觉信息都必须通过它才能进入感觉新皮层。 丘脑核团的单个神经元以两种不同的模式工作：“中继”模式和“突发”模式。 中继模式主要发生在警觉状态下，通过丘脑的突触传递非常有效。 相比之下，爆发模式主要与注意力不集中、困倦和睡眠有关，并且通过丘脑的突触传递受到抑制。 相当大的努力已经进入了解这些丘脑模式的机制及其在感知中的作用，丘脑爆发已与注意力机制。 然而，在我们理解丘脑爆发的感知后果方面，一个关键的环节仍然没有被探索：我们不知道丘脑冲动在丘脑皮质突触处爆发的命运。 我们可以预期突触效能的降低，如在爆发模式期间在视网膜膝状体突触处发生的，或者爆发性丘脑冲动激活新皮层回路的效能的增加。 我们的初步工作表明，在突触的影响，丘脑皮质爆发一类皮质抑制性神经元内体感“桶”皮层的有效增强。 拟议的实验将通过以下方式扩展这些结果：（a）检查爆发性丘脑皮质冲动对不同行为/EEG状态期间研究的兴奋性皮质群体的影响，以及（B）检查由丘脑爆发引起的兴奋的皮质内传播。 所有实验将使用新型细胞外和细胞内多电极方法在清醒受试者中进行。 丘脑皮质投射神经元和皮层神经元的活动在S1桶内的不同类别将同时进行研究，这些确定的神经元之间的相互作用将使用互相关，尖峰触发平均突触后电位，和电流源密度分析的方法进行分析。 我们假设，爆发丘脑冲动产生一个增强的丘脑皮质和皮质内传播的兴奋。 这些数据将提供一个独特的看法，在自然条件下，在清醒状态下研究丘脑皮质网络。

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.