New Circuit Model Offers Insights into Brain Function
Scientists at EPFL’s Blue Brain Project have developed a groundbreaking computational model of the thalamic microcircuit in the mouse brain, offering new insights into the role this region plays in brain function and dysfunction.
The thalamus and thalamic reticular nucleus are situated at the heart of the mammalian brain and are known to play a key role in a wide range of functions, including the transmission of sensory information to the cortex and the transition between brain states such as sleep and wakefulness. However, alterations in thalamic neuron firing and interconnectivity have been linked to pathological brain rhythms and changes in the rhythmic brain waves that occur during sleep, which have been observed in disorders such as schizophrenia, neurodevelopmental disorders, attention deficit hyperactivity disorder, and Alzheimer’s disease.
The new model developed by Blue Brain is the first to capture the complex shapes and biophysical properties of 14,000 neurons connected by 6 million synapses. It can be used to explore the structural and functional complexity of neural circuits. The model also replicates multiple independent network-level experimental findings across different brain states, and provides a novel unifying cellular and synaptic account of spontaneous and evoked activity in both wakefulness and sleep.
One of the key findings of the study is that inhibitory rebound, a process that helps to regulate the activity of nerve cells, produces an enhancement of thalamic responses during wakefulness at certain frequencies. The model also showed that thalamic interactions generate the characteristic waxing and waning of spindle oscillations, the rhythmic brain waves seen during sleep, and that changes in the excitability of thalamic cells control the frequency and occurrence of these spindle oscillations.
“This is particularly relevant to interpreting the presence or absence of spindles in different brain disorders,” emphasizes first author Dr. Elisabetta Iavarone. “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,” adds Blue Brain Project Founder and Director, Prof. Henry Markram.
“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,” explains Prof. Sean Hill, co-director of the Blue Brain Project and the Scientific Director of the Krembil Centre for Neuroinformatics.
The research, published in the latest issue of Cell Reports, represents a significant step forward in understanding the role of the thalamus and thalamic reticular nucleus in brain function and dysfunction, and the model developed by the Blue Brain Project at EPFL is now accessible for researchers to use in their own studies.
“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,” concludes Hill.
For more information, please contact: Blue Brain Communications - [email protected]
About EPFL’s Blue Brain Project
The aim of the EPFL Blue Brain Project, a Swiss brain research initiative founded and directed by Professor Henry Markram, is to establish simulation neuroscience as a complementary approach alongside experimental, theoretical and clinical neuroscience to understanding the brain, by building the world’s first biologically detailed digital reconstructions and simulations of the mouse brain.
EPFL, one of the two Swiss Federal Institutes of Technology, based in Lausanne, is Europe’s most cosmopolitan technical university with students, professors and staff from over 120 nations. A dynamic environment, open to Switzerland and the world, EPFL is centered on its three missions: teaching, research and technology transfer. EPFL works together with an extensive network of partners including other universities and institutes of technology, developing and emerging countries, secondary schools and colleges, industry and economy, political circles and the general public, to bring about real impact for society.
This study was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne (EPFL), from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology, with additional funding from the Krembil Foundation and funds from the European Union’s Horizon 2020 Research and Innovation Program, European Commission (Grant Agreements No. HBP SGA2 785907 and SGA3 945539) and Ministerio de Ciencia e Innovación FLAG-ERA grant NeuronsReunited (MICINN-AEI PCI2019-111900-2).
Thalamoreticular Microcircuit Portal
Iavarone, E., Simko, J., Shi, Y., Bertschy, M., García-Amado, M., Litvak, P., Kaufmann, A.-K., O’Reilly, C., Amsalem, O., Abdellah, M., Chevtchenko, G., Coste, B., Courcol, J.-D., Ecker, A., Favreau, C., Fleury, A. C., Van Geit, W., Gevaert, M., Guerrero, N. R, Herttuainen, J., Ivaska, G., Kerrien, S., King, J.G., Kumbhar, P., Lurie, P., Magkanaris, I., Muddapu, V.R., Nair, J., Pereira, F.L., Perin, R., Petitjean, F., Ranjan, R., Reimann, M., Soltuzu, L., Sy, M.F., Tuncel, M.A., Ulbrich, A., Wolf, M., Clascá, F., Markram, H., & Hill, S. L. (2023). Thalamic control of sensory processing and spindles in a biophysical somatosensory thalamoreticular circuit model of wakefulness and sleep. Cell Reports, 42(3), 112200. https://doi.org/10.1016/j.celrep.2023.112200