Single-pulse stimulation of cerebellar nuclei stops epileptic thalamic activity
| Autor: | Peter Holland, Sade J. Faneyte, Lieke Kros, Oscar H J Eelkman Rooda, Nico A Jansen, Freek E. Hoebeek, Else A. Tolner, Arn M. J. M. van den Maagdenberg, Chris I. De Zeeuw, Huub J Poelman, Simona V. Gornati |
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| Přispěvatelé: | Neurosurgery, Neurosciences, Netherlands Institute for Neuroscience (NIN) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cerebellum
Thalamus Biophysics Stimulation Neurosciences. Biological psychiatry. Neuropsychiatry Optogenetics 050105 experimental psychology Mice 03 medical and health sciences Epilepsy 0302 clinical medicine Genetic model medicine Animals 0501 psychology and cognitive sciences Ictal Cerebral Cortex Neurons Chemistry General Neuroscience 05 social sciences Generalized absence seizures medicine.disease medicine.anatomical_structure Cerebellar Nuclei Epilepsy Absence nervous system Cerebral cortex Thalamic Nuclei Optogenetic neurostimulation Neurology (clinical) Neuroscience 030217 neurology & neurosurgery RC321-571 |
| Zdroj: | Brain Stimulation, 14(4), 861-872. Elsevier Inc. Brain Stimulation, 14, 861-872. Elsevier B.V. Brain Stimulation, Vol 14, Iss 4, Pp 861-872 (2021) Brain Stimulation, 14(4), 861-872. ELSEVIER SCIENCE INC |
| ISSN: | 1935-861X |
| Popis: | Background: Epileptic (absence) seizures in the cerebral cortex can be stopped by pharmacological and optogenetic stimulation of the cerebellar nuclei (CN) neurons that innervate the thalamus. However, it is unclear how such stimulation can modify underlying thalamo-cortical oscillations. Hypothesis: Here we tested whether rhythmic synchronized thalamo-cortical activity during absence seizures can be desynchronized by single-pulse optogenetic stimulation of CN neurons to stop seizure activity. Methods: We performed simultaneous thalamic single-cell and electrocorticographical recordings in awake tottering mice, a genetic model of absence epilepsy, to investigate the rhythmicity and synchronicity. Furthermore, we tested interictally the impact of single-pulse optogenetic CN stimulation on thalamic and cortical recordings. Results: We show that thalamic firing is highly rhythmic and synchronized with cortical spike-and-wave discharges during absence seizures and that this phase-locked activity can be desynchronized upon single-pulse optogenetic stimulation of CN neurons. Notably, this stimulation of CN neurons was more effective in stopping seizures than direct, focal stimulation of groups of afferents innervating the thalamus. During interictal periods, CN stimulation evoked reliable but heterogeneous responses in thalamic cells in that they could show an increase or decrease in firing rate at various latencies, bi-phasic responses with an initial excitatory and subsequent inhibitory response, or no response at all. Conclusion: Our data indicate that stimulation of CN neurons and their fibers in thalamus evokes differential effects in its downstream pathways and desynchronizes phase-locked thalamic neuronal firing during seizures, revealing a neurobiological mechanism that may explain how cerebellar stimulation can stop seizures. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND |
| Databáze: | OpenAIRE |
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