Elisabetta Iavarone¹, Jane Simko², Ying Shi^1,2, Marine Bertschy², María García-Amado³, Polina Litvak¹, Anna-Kristin Kaufmann¹, Christian O’Reilly¹, Oren Amsalem⁴, Marwan Abdellah¹, Grigori Chevtchenko¹, Benoît Coste¹, Jean-Denis Courcol¹, András Ecker¹, Cyrille Favreau¹, Adrien Christian Fleury¹, Werner Van Geit¹, Michael Gevaert¹, Nadir Román Guerrero¹, Joni Herttuainen¹, Genrich Ivaska¹, Samuel Kerrien¹, James G. King¹, Pramod Kumbhar¹, Patrycja Lurie¹, Ioannis Magkanaris¹, Vignayanandam Ravindernath Muddapu¹, Jayakrishnan Nair¹, Fernando L. Pereira¹, Rodrigo Perin², Fabien Petitjean¹, Rajnish Ranjan¹, Michael Reimann¹, Liviu Soltuzu¹, Mohameth François Sy¹, M. Anıl Tuncel¹, Alexander Ulbrich¹, Matthias Wolf¹, Francisco Clascà³, Henry Markram^1,2 and Sean L. Hill^1,5,6,7

¹Blue Brain Project, École polytechnique fédérale de Lausanne (EPFL), Geneva, Switzerland
²Laboratory of Neural Microcircuitry (LNMC), École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland
³Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Spain
⁴Department of Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
⁵Department of Psychiatry, University of Toronto, Canada
⁶Department of Physiology, University of Toronto, Canada
⁷Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health (CAMH), Toronto, Canada

Abstract

Thalamoreticular circuitry plays a key role in arousal, attention, cognition, and sleep spindles, and is linked to several brain disorders. A detailed computational model of mouse somatosensory thalamus and thalamic reticular nucleus has been developed to capture the properties of over 14,000 neurons connected by 6 million synapses. The model recreates the biological connectivity of these neurons and simulations of the model reproduce multiple experimental findings in different brain states. The model shows that inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness. We find that thalamic interactions are responsible for the characteristic waxing and waning of spindle oscillations. In addition, we find that changes in thalamic excitability control spindle frequency and their incidence. The model is made openly available to provide a new tool for studying the function and dysfunction of the thalamoreticular circuitry in various brain states.

Journal Article DOI

https://doi.org/10.1016/j.celrep.2023.112200

Associated Scientific Publications

• Iavarone, E., Yi, J., Shi, Y., Zandt, B. J., O’Reilly, C., Van Geit, W., … & Hill, S. L. (2019). Experimentally-constrained biophysical models of tonic and burst firing modes in thalamocortical neurons. PLoS Computational Biology, 15(5), e1006753. doi: 10.1371/journal.pcbi.1006753
• Iavarone, E. (2020). A computational biophysical model of thalamic and reticular nucleus microcircuitry: from neurons to emergent network dynamics (THESIS No. 7472). EPFL. doi: 10.5075/epfl-thesis-7472
• O’Reilly, C., Iavarone, E., Yi, J., & Hill, S. L. (2021). Rodent somatosensory thalamocortical circuitry: neurons, synapses, and connectivity. Neuroscience & Biobehavioral Reviews. doi: 10.1016/j.neubiorev.2021.03.015

About this Studio

This Blue Brain Project (BBP) Nexus Studio is a public resource associated with the release of the first biologically-detailed model of a thalamic microcircuit. It is a resource for the community to explore how the BBP reconstruction workflow developed for the neocortex (Markram et al., 2015) has been adapted to model another brain region.

In this Studio, it is possible to download experimental data used for model building and validation, neuron models, circuit model in sonata format, and videos of network simulations. Note that in this Studio, we use the ME-type names “cAD_noscltb” instead of Rt_RC’s “cAD_ltb”, “cNAD_noscltb” instead of Rt_RC’s “cNAD_ltb”, “dAD_ltb” instead of VPL_TC’s “cAD_ltb”, and “dNAD_ltb” instead of VPL_TC’s “cNAD_ltb”.

Data Licenses

• Wenzhou Medical University: CC BY-NC-SA 4.0
• Howard Hughes Medical Institute: CC-BY NC 4.0
• Autonomous University of Madrid: CC-BY NC 4.0
• École Polytechnique Fédérale de Lausanne: CC-BY NC 4.0

Graphical Abstract