Mechanisms for state-dependent changes of thalamic processing

Thalamus contains nuclei in sensory and motor systems that control the major gateways to cerebral cortex in a two-way dialogue with cortex. The nuclei pre-process, synchronize and modulate cortical input depending on behavioral states like sleep, wakefuln ess, arousal, and vigilance. In awake, attentive states the nuclei perform highly specific dynamic signal processing of afferent pre-thalamic input, and amplify putative important information and attenuate putative less important information, whereas in s tates of slow-wave sleep the nuclei generate slow, synchronized activity that to a large extent blocks transmission of signals from the pre-thalamic structures to cortex. The specific aims of this proposal are investigation of mechanisms related to state- dependent shifts in thalamic processing using the thalamic nucleus of the visual pathway (LGN) as model system. We will focus on two major topics. First the physiology of local interneurons which today are the least well understood type of neuron in thala mic relay nuclei. The interneurons in LGN receive their primary input from retina and mediate feedforward inhibition to the thalamic neurons that project to visual cortex. We focus on signal processing in the dendrites of the interneurons, and on mechanis ms that change this processing according to behavioral states. We will use a recently developed optical imaging technique (calcium imaging and multi-photon microscopy) that makes it possible to visualize directly dendritic activity in the interneurons and thereby get important new insight into how the interneurons operate during different states. Second, we will study cortical feedback mechanisms that control the thalamic processing, presumably by shifting the effect of the feedback between facilitation a nd suppression depending on behavioural states.