Completed Brain & Nervous System Psychology & Behaviour

Mechanism of physiological thalamocortical rhythms.

In plain English

AI plain-English summary

Every second of every day, the brain generates electrical rhythms that shift between sleep and wakefulness—and this project will map the cellular machinery inside the thalamus that drives those rhythms. The thalamus acts as a relay station for sensory information and a hub for brain-wide communication, yet the precise rules by which its cells and synapses generate specific EEG rhythms—such as the alpha rhythm of relaxed wakefulness and the slow (<1 Hz) rhythm of deep sleep—remain poorly understood. This project fills that gap by combining recordings from single neurons, calcium imaging of dendrites, and large-scale recordings from hundreds of neurons in freely moving, naturally sleeping and waking animals. This is fundamental science. It will not produce a new drug or device tomorrow. But understanding how thalamic circuits normally generate these rhythms is essential for interpreting what goes wrong in neurological disorders—such as epilepsy, schizophrenia, or chronic pain—where thalamic function is altered. Past discoveries about how brain rhythms arise have led to treatments like deep brain stimulation and sleep therapies. A full mechanistic picture of thalamic computation could similarly open new routes for diagnosing or correcting rhythm disruptions in disease.

View original technical description
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.

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Researchers

Vincenzo Crunelli (EPMC Awardee)

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Original classification

Programme Grant

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