Mechanism of physiological thalamocortical rhythms. (360G-Wellcome-091882_Z_10_Z)

The aim of this project is to understand the cellular, synaptic and network rules that govern thalamic physiology, and how they coalesce within cortico-thalamo-cortical modules to bring about EEG rhythms of different vigilance states. We will use a multidisciplinary approach that includes somatic single and paired recordings as well as somato-dendritic calcium imaging in vitro, intracellular recordings in vivo, and large neuronal ensemble recordings in freely moving, naturally waking-sleeping an imals. Specifically, we will determine: 1 - the cell-specificity of the firing dynamics of thalamocortical neurons and the physiology and pharmacology of intranuclear thalamic synapses; 2 - the dendritic mechanisms underlying the integration of sensory and cortical signals in thalamocortical neurons; 3 - the input-specificity, modulation by thalamic transmitters and physiological role of the tonic GABAA receptor-mediated inhibition of thalamocortical neurons; 4 - the spatio-temporal firing dynamics of simultaneously recorded large thalamic and cortical populations during two behaviourally significant EEG waves: the alpha rhythm and the slow ( < 1Hz) sleep rhythm. By establishing a full mechanistic picture of thalamic computation during different behavioural states, this study will further our knowledge of subcortical sensory processing and higher frequency cortico-thalamic network rhythms, and thus help our understanding of thalamic alterations in neurological disorders.