Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition
Parvalbumin-positive (PV+) γ-aminobutyric acid (GABA) interneurons are critically involved in producing rapid network oscillations and cortical microcircuit computations, but the significance of PV+ axon myelination to the temporal features of inhibition remains elusive. Here, using toxic and geneti...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/73827 |
| _version_ | 1828108850121670656 |
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| author | Mohit Dubey Maria Pascual-Garcia Koke Helmes Dennis D Wever Mustafa S Hamada Steven A Kushner Maarten HP Kole |
| author_facet | Mohit Dubey Maria Pascual-Garcia Koke Helmes Dennis D Wever Mustafa S Hamada Steven A Kushner Maarten HP Kole |
| author_sort | Mohit Dubey |
| collection | DOAJ |
| description | Parvalbumin-positive (PV+) γ-aminobutyric acid (GABA) interneurons are critically involved in producing rapid network oscillations and cortical microcircuit computations, but the significance of PV+ axon myelination to the temporal features of inhibition remains elusive. Here, using toxic and genetic mouse models of demyelination and dysmyelination, respectively, we find that loss of compact myelin reduces PV+ interneuron presynaptic terminals and increases failures, and the weak phasic inhibition of pyramidal neurons abolishes optogenetically driven gamma oscillations in vivo. Strikingly, during behaviors of quiet wakefulness selectively theta rhythms are amplified and accompanied by highly synchronized interictal epileptic discharges. In support of a causal role of impaired PV-mediated inhibition, optogenetic activation of myelin-deficient PV+ interneurons attenuated the power of slow theta rhythms and limited interictal spike occurrence. Thus, myelination of PV axons is required to consolidate fast inhibition of pyramidal neurons and enable behavioral state-dependent modulation of local circuit synchronization. |
| first_indexed | 2024-04-11T10:52:24Z |
| format | Article |
| id | doaj.art-c38a3231f3e9473d86fdc1d41c3ed498 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:52:24Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c38a3231f3e9473d86fdc1d41c3ed4982022-12-22T04:28:52ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.73827Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibitionMohit Dubey0https://orcid.org/0000-0001-9770-0633Maria Pascual-Garcia1Koke Helmes2Dennis D Wever3Mustafa S Hamada4https://orcid.org/0000-0002-2232-6146Steven A Kushner5https://orcid.org/0000-0002-9777-3338Maarten HP Kole6https://orcid.org/0000-0002-3883-5682Department of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, NetherlandsDepartment of Psychiatry, Erasmus Medical Centre, Rotterdam, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, Netherlands; Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsDepartment of Psychiatry, Erasmus Medical Centre, Rotterdam, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, Netherlands; Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsParvalbumin-positive (PV+) γ-aminobutyric acid (GABA) interneurons are critically involved in producing rapid network oscillations and cortical microcircuit computations, but the significance of PV+ axon myelination to the temporal features of inhibition remains elusive. Here, using toxic and genetic mouse models of demyelination and dysmyelination, respectively, we find that loss of compact myelin reduces PV+ interneuron presynaptic terminals and increases failures, and the weak phasic inhibition of pyramidal neurons abolishes optogenetically driven gamma oscillations in vivo. Strikingly, during behaviors of quiet wakefulness selectively theta rhythms are amplified and accompanied by highly synchronized interictal epileptic discharges. In support of a causal role of impaired PV-mediated inhibition, optogenetic activation of myelin-deficient PV+ interneurons attenuated the power of slow theta rhythms and limited interictal spike occurrence. Thus, myelination of PV axons is required to consolidate fast inhibition of pyramidal neurons and enable behavioral state-dependent modulation of local circuit synchronization.https://elifesciences.org/articles/73827parvalbumin interneurondemyelinationneocortex |
| spellingShingle | Mohit Dubey Maria Pascual-Garcia Koke Helmes Dennis D Wever Mustafa S Hamada Steven A Kushner Maarten HP Kole Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition eLife parvalbumin interneuron demyelination neocortex |
| title | Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition |
| title_full | Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition |
| title_fullStr | Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition |
| title_full_unstemmed | Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition |
| title_short | Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition |
| title_sort | myelination synchronizes cortical oscillations by consolidating parvalbumin mediated phasic inhibition |
| topic | parvalbumin interneuron demyelination neocortex |
| url | https://elifesciences.org/articles/73827 |
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