Impact of Thalamic Impulses On Awake Neocortex

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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.