Impact of Thalamic Impulses On Awake Neocortex

这一建议旨在了解丘脑皮质感觉信息在不同行为状态下进入新皮质网络并被处理的机制。哺乳动物的背丘脑是一个门户，所有的感觉信息，除了嗅觉，必须通过它才能进入感觉新皮层。丘脑核的单个神经元以两种不同的模式运作：“接力”模式和“爆发”模式。传递模式主要发生在警觉状态，通过丘脑的突触传递是非常有效的。相反，突发模式主要与注意力不集中、嗜睡和睡眠有关，并且通过丘脑的突触传递受到抑制。在理解这些丘脑模式的潜在机制及其在感知中的作用方面，人们付出了相当大的努力，丘脑的爆发与注意力的机制有关。然而，在我们对丘脑爆发的感知后果的理解中，一个至关重要的环节仍未被探索：我们不知道丘脑皮质突触中丘脑冲动爆发的命运。我们可以预期，要么是突触效能的降低，就像在爆发模式下视网膜-胫状突触发生的那样，要么是丘脑脉冲爆发激活新皮层回路时效能的提高。我们的初步工作表明，丘脑皮层爆发对体感“桶”皮层内一类皮层抑制神经元的突触影响有强有力的增强。拟议的实验将通过(a)检查在不同行为/脑电图状态下研究的突发丘脑皮质脉冲对兴奋性皮质种群的影响，以及(b)检查丘脑脉冲引起的兴奋在皮层内的传播来扩展这些结果。所有的实验将在清醒的受试者中进行，使用新颖的细胞外和细胞内多电极方法。将同时研究S1桶内不同类别的丘脑皮质投射神经元和皮质神经元的活动，并使用相互关联、突触后电位的峰值触发平均和电流源密度分析等方法分析这些已识别神经元之间的相互作用。我们假设爆发的丘脑脉冲产生增强的丘脑皮质和皮质内的兴奋扩散。这些数据将为在清醒状态下的自然条件下研究丘脑皮质网络提供一个独特的视角。

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.