PT  - JOURNAL ARTICLE
AU  - Elisabetta Iavarone
AU  - Jane Simko
AU  - Ying Shi
AU  - Marine Bertschy
AU  - María García-Amado
AU  - Polina Litvak
AU  - Anna-Kristin Kaufmann
AU  - Christian O’Reilly
AU  - Oren Amsalem
AU  - Marwan Abdellah
AU  - Grigori Chevtchenko
AU  - Benoît Coste
AU  - Jean-Denis Courcol
AU  - András Ecker
AU  - Cyrille Favreau
AU  - Adrien Christian Fleury
AU  - Werner Van Geit
AU  - Michael Gevaert
AU  - Nadir Román Guerrero
AU  - Joni Herttuainen
AU  - Genrich Ivaska
AU  - Samuel Kerrien
AU  - James G. King
AU  - Pramod Kumbhar
AU  - Patrycja Lurie
AU  - Ioannis Magkanaris
AU  - Vignayanandam Ravindernath Muddapu
AU  - Jayakrishnan Nair
AU  - Fernando L. Pereira
AU  - Rodrigo Perin
AU  - Fabien Petitjean
AU  - Rajnish Ranjan
AU  - Michael Reimann
AU  - Liviu Soltuzu
AU  - Mohameth François Sy
AU  - M. Anıl Tuncel
AU  - Alexander Ulbrich
AU  - Matthias Wolf
AU  - Francisco Clascá
AU  - Henry Markram
AU  - Sean L. Hill
TI  - Thalamic control of sensory enhancement and sleep spindle properties in a biophysical model of thalamoreticular microcircuitry
AID  - 10.1101/2022.02.28.482273
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.28.482273
4099  - http://biorxiv.org/content/early/2022/04/14/2022.02.28.482273.short
4100  - http://biorxiv.org/content/early/2022/04/14/2022.02.28.482273.full
AB  - Thalamoreticular circuitry is known to play a key role in attention, cognition and the generation of sleep spindles, and is implicated in numerous brain disorders, but the cellular and synaptic mechanisms remain intractable. Therefore, we developed the first detailed computational model of mouse thalamus and thalamic reticular nucleus microcircuitry that captures morphological and biophysical properties of ∼14,000 neurons connected via ∼6M synapses, and recreates biological synaptic and gap junction connectivity. Simulations recapitulate multiple independent network-level experimental findings across different brain states, providing a novel unifying cellular and synaptic account of spontaneous and evoked activity in both wakefulness and sleep. Furthermore, we found that: 1.) inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness, in addition to its role in spindle generation; 2.) thalamic interactions generate the characteristic waxing and waning of spindle oscillations; and 3.) changes in thalamic excitability (e.g. due to neuromodulation) control spindle frequency and occurrence. The 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.Competing Interest StatementThe authors have declared no competing interest.