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

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 gene...

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Main Authors: 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, Irene Rembado
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58717-2
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author 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
Irene Rembado
author_facet 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
Irene Rembado
author_sort Simone Russo
collection DOAJ
description 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.
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series Nature Communications
spelling doaj-art-1c2b6765ae17487d97a3a9da79ce4a982025-08-20T03:26:43ZengNature PortfolioNature Communications2041-17232025-04-0116111910.1038/s41467-025-58717-2Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humansSimone Russo0Leslie D. Claar1Giulia Furregoni2Lydia C. Marks3Giri Krishnan4Flavia Maria Zauli5Gabriel Hassan6Michela Solbiati7Piergiorgio d’Orio8Ezequiel Mikulan9Simone Sarasso10Mario Rosanova11Ivana Sartori12Maxim Bazhenov13Andrea Pigorini14Marcello Massimini15Christof Koch16Irene Rembado17Department of Biomedical and Clinical Sciences, Università degli Studi di MilanoBrain and Consciousness, Allen InstituteDepartment of Biomedical and Clinical Sciences, Università degli Studi di MilanoBrain and Consciousness, Allen InstituteDepartment of Medicine, University of California San DiegoDepartment of Biomedical and Clinical Sciences, Università degli Studi di MilanoDepartment of Biomedical and Clinical Sciences, Università degli Studi di MilanoDepartment of Biomedical and Clinical Sciences, Università degli Studi di MilanoASST Grande Ospedale Metropolitano Niguarda, “C. Munari” Epilepsy Surgery CentreDepartment of Health Sciences, University of MilanDepartment of Biomedical and Clinical Sciences, Università degli Studi di MilanoDepartment of Biomedical and Clinical Sciences, Università degli Studi di MilanoASST Grande Ospedale Metropolitano Niguarda, “C. Munari” Epilepsy Surgery CentreDepartment of Medicine, University of California San DiegoDepartment of Biomedical, Surgical and Dental Sciences, Università degli Studi di MilanoDepartment of Biomedical and Clinical Sciences, Università degli Studi di MilanoBrain and Consciousness, Allen InstituteBrain and Consciousness, Allen InstituteAbstract 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.https://doi.org/10.1038/s41467-025-58717-2
spellingShingle 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
Irene Rembado
Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans
Nature Communications
title Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans
title_full Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans
title_fullStr Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans
title_full_unstemmed Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans
title_short Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans
title_sort thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans
url https://doi.org/10.1038/s41467-025-58717-2
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