A new circuit model provides new insights into brain function

A groundbreaking computational model of the thalamic microcircuit in the mouse brain.

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The thalamus and thalamic reticular nucleus (Rt) is at the heart of the mammalian brain’s thalamocortical (TC) system. Thalamic relay cells form excitatory collaterals with thalamic reticular neurons and send projections to the cortex. The thalamoreticular circuit is created when these neurons return inhibitory predictions to the thalamus.

The Blue Brain Project at EPFL has created a groundbreaking computational model of the thalamic microcircuit in the mouse brain, providing new insights into the role of this region in brain function and dysfunction.

The thalamus and thalamic reticular nucleus are located at the heart of the mammalian brain

They are known to play a key role in various functions, including sensory information transmission to the cortex and brain state transitions such as sleep and wakefulness. Changes in thalamic neuron firing and interconnectivity, on the other hand, have been linked to pathological brain rhythms and changes in the rhythmic brain waves that occur during sleep, as seen in disorders such as schizophrenia, neurodevelopmental disorders, attention deficit hyperactivity disorder, and Alzheimer’s disease.

The model reproduces multiple independent network-level experimental findings across different brain states by capturing the complex shapes and biophysical properties of 14,000 neurons connected by 6 million synapses. It also offers a novel cellular and synaptic account of spontaneous and evoked activity in wakefulness and sleep.

The study discovered that inhibitory rebound, a process that helps regulate nerve cell activity, enhances thalamic responses during wakefulness at specific frequencies and that thalamic interactions produce the characteristic waxing and waning of spindle oscillations, the rhythmic brain waves seen during sleep.

Elisabetta Iavarone, Blue Brain Project Founder and Director Henry Markram, said, “This is particularly relevant to interpreting the presence or absence of spindles in different brain disorders. This approach yielded the first morphologically and biophysically-detailed model of a thalamic microcircuit, demonstrating that the modeling strategy Blue Brain developed for cortical microcircuitry can be applied to other brain regions.” 

Sean Hill, co-director of the Blue Brain Project and the Scientific Director of the Krembil Centre for Neuroinformatics, explains, “Computer models and simulations can facilitate the integration and standardization of different sources of experimental data, highlight key missing experiments, and at the same time provide a tool to test hypotheses and explore the structural and functional complexity of neural circuits.” 

The study, published in the most recent issue of Cell Reports, represents a significant advance in understanding the role of the thalamus and thalamic reticular nucleus in brain function and dysfunction. And the Blue Brain Project model developed at EPFL is now available for researchers to use in their studies.

Concludes Hill Said, “This model is openly available and provides a new tool to interpret spindle oscillations and test hypotheses of thalamoreticular circuit function and dysfunction across different network states in health and disease.” 

The Swiss government’s ETH Board of the Swiss Federal Institutes of Technology funded the Blue Brain Project, a research center of the École Polytechnique fédérale de Lausanne (EPFL).

Journal Reference:

  1. Jane Simko, Elisabetta Iavarone, etal.Thalamic control of sensory processing and spindles in a biophysical somatosensory thalamoreticular circuit model of wakefulness and sleep. Cell Reports. DOI: 10.1016/j.celrep.2023.112200
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