Mar 3, 2023

Thalamic Control of Sensory Processing and Spindles in a Biophysical Somatosensory Thalamoreticular Circuit Model of Wakefulness and Sleep

Elisabetta Iavarone, Jane Simko, Ying Shi, Marine Bertschy, María García-Amado, Polina Litvak, Anna-Kristin Kaufmann, Christian O’Reilly, Oren Amsalem, Marwan Abdellah, Grigori Chevtchenko, Benoît Coste, Jean-Denis Courcol, András Ecker, Cyrille Favreau, Adrien Christian Fleury, Werner Van Geit, Michael Gevaert, Nadir Román Guerrero, Joni Herttuainen, Genrich Ivaska, Samuel Kerrien, James G. King, Pramod Kumbhar, Patrycja Lurie, Ioannis Magkanaris, Vignayanandam Ravindernath Muddapu, Jayakrishnan Nair, Fernando L. Pereira, Rodrigo Perin, Fabien Petitjean, Rajnish Ranjan, Michael Reimann, Liviu Soltuzu, Mohameth François Sy, M. Anıl Tuncel, Alexander Ulbrich, Matthias Wolf, Francisco Clascá, Henry Markram, and Sean L. Hill, Cell Reports 2023, Volume 42, Issue 3, Article No. 112200, online 24 February 2023; doi: 10.1016/j.celrep.2023.112200

Thalamoreticular circuitry, characterized in part by the sleep spindle – a brain rhythm that is most prominently visible in the electroencephalogram (EEG) during stage 2 sleep (light sleep) – plays a key role in arousal, attention, and cognition and is linked to several brain disorders. We developed a detailed computational model of mouse somatosensory thalamus and thalamic reticular nucleus to capture the properties of over 14,000 neurons connected by 6 million synapses. The model recreates the biological connectivity of these neurons, and, in simulations, the model reproduces multiple experimental findings in different brain states. The simulations show 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 sleep spindle oscillations. Additionally, we find that changes in thalamic excitability control spindle frequency and incidence. The model has been made openly available to provide a new tool for studying function and dysfunction in the thalamoreticular circuitry of various brain states.

The scientific and technical impact of the study can be summarized as:

  • A computational model of thalamoreticular microcircuitry consisting of physiologically and morphologically detailed neuron models and their connections is presented and has been made publicly available
  • Inhibitory rebounds, a spiking behavior exhibited by specific ion channels present in the thalamus, lead to a frequency-specific enhancement of sensory responses
  • Interactions within the thalamus produce distinctive waxing and waning of sleep spindle oscillations
  • Alterations in thalamic excitability, e.g., in terms of neuron membrane potential, influence the frequency and occurrence of spindle oscillations