Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans

Simone Russo, Leslie D. Claar, Giulia Furregoni, Lydia C. Marks, Giri Krishnan, Flavia Maria Zauli, Gabriel Hassan, Michela Solbiati, Piergiorgio d’Orio, Ezequiel Mikulan, Simone Sarasso, Mario Rosanova, Ivana Sartori, Maxim Bazhenov, Andrea Pigorini, Marcello Massimini, Christof Koch and Irene Rembado ()
Additional contact information
Simone Russo: Università degli Studi di Milano
Leslie D. Claar: Allen Institute
Giulia Furregoni: Università degli Studi di Milano
Lydia C. Marks: Allen Institute
Giri Krishnan: University of California San Diego
Flavia Maria Zauli: Università degli Studi di Milano
Gabriel Hassan: Università degli Studi di Milano
Michela Solbiati: Università degli Studi di Milano
Piergiorgio d’Orio: “C. Munari” Epilepsy Surgery Centre
Ezequiel Mikulan: University of Milan
Simone Sarasso: Università degli Studi di Milano
Mario Rosanova: Università degli Studi di Milano
Ivana Sartori: “C. Munari” Epilepsy Surgery Centre
Maxim Bazhenov: University of California San Diego
Andrea Pigorini: Università degli Studi di Milano
Marcello Massimini: Università degli Studi di Milano
Christof Koch: Allen Institute
Irene Rembado: Allen Institute

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Cortical stimulation with single pulses is a common technique in clinical practice and research. However, we still do not understand the extent to which it engages subcortical circuits that may contribute to the associated evoked potentials (EPs). Here we show that cortical stimulation generates remarkably similar EPs in humans and mice, with a late component similarly modulated by the state of the targeted cortico-thalamic network. We then optogenetically dissect the underlying circuit in mice, demonstrating that the EPs late component is caused by a thalamic hyperpolarization and rebound. The magnitude of this late component correlates with bursting frequency and synchronicity of thalamic neurons, modulated by the subject’s behavioral state. A simulation of the thalamo-cortical circuit highlights that both intrinsic thalamic currents as well as cortical and thalamic GABAergic neurons contribute to this response profile. We conclude that single pulse cortical stimulation engages cortico-thalamo-cortical circuits largely preserved across different species and stimulation modalities.

Date: 2025
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DOI: 10.1038/s41467-025-58717-2

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