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Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity

Elevated states of brain plasticity typical for critical periods of early postnatal life can be reinstated in the adult brain through interventions, such as antidepressant treatment and environmental enrichment, and induced plasticity may be critical for the antidepressant action. Parvalbumin-positi...

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Autores principales: Winkel, Frederike, Ryazantseva, Maria, Voigt, Mathias B., Didio, Giuliano, Lilja, Antonia, Llach Pou, Maria, Steinzeig, Anna, Harkki, Juliana, Englund, Jonas, Khirug, Stanislav, Rivera, Claudio, Palva, Satu, Taira, Tomi, Lauri, Sari E., Umemori, Juzoh, Castrén, Eero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872988/
https://www.ncbi.nlm.nih.gov/pubmed/34321594
http://dx.doi.org/10.1038/s41380-021-01211-0
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author Winkel, Frederike
Ryazantseva, Maria
Voigt, Mathias B.
Didio, Giuliano
Lilja, Antonia
Llach Pou, Maria
Steinzeig, Anna
Harkki, Juliana
Englund, Jonas
Khirug, Stanislav
Rivera, Claudio
Palva, Satu
Taira, Tomi
Lauri, Sari E.
Umemori, Juzoh
Castrén, Eero
author_facet Winkel, Frederike
Ryazantseva, Maria
Voigt, Mathias B.
Didio, Giuliano
Lilja, Antonia
Llach Pou, Maria
Steinzeig, Anna
Harkki, Juliana
Englund, Jonas
Khirug, Stanislav
Rivera, Claudio
Palva, Satu
Taira, Tomi
Lauri, Sari E.
Umemori, Juzoh
Castrén, Eero
author_sort Winkel, Frederike
collection PubMed
description Elevated states of brain plasticity typical for critical periods of early postnatal life can be reinstated in the adult brain through interventions, such as antidepressant treatment and environmental enrichment, and induced plasticity may be critical for the antidepressant action. Parvalbumin-positive (PV) interneurons regulate the closure of developmental critical periods and can alternate between high and low plasticity states in response to experience in adulthood. We now show that PV plasticity states and cortical networks are regulated through the activation of TrkB neurotrophin receptors. Visual cortical plasticity induced by fluoxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant, was lost in mice with reduced expression of TrkB in PV interneurons. Conversely, optogenetic gain-of-function studies revealed that activation of an optically activatable TrkB (optoTrkB) specifically in PV interneurons switches adult cortical networks into a state of elevated plasticity within minutes by decreasing the intrinsic excitability of PV interneurons, recapitulating the effects of fluoxetine. TrkB activation shifted cortical networks towards a low PV configuration, promoting oscillatory synchrony, increased excitatory-inhibitory balance, and ocular dominance plasticity. OptoTrkB activation promotes the phosphorylation of Kv3.1 channels and reduces the expression of Kv3.2 mRNA providing a mechanism for the lower excitability. In addition, decreased expression and puncta of Synaptotagmin2 (Syt2), a presynaptic marker of PV interneurons involved in Ca(2+)-dependent neurotransmitter release, suggests lower inputs onto pyramidal neurons suppressing feed-forward inhibition. Together, the results provide mechanistic insights into how TrkB activation in PV interneurons orchestrates the activity of cortical networks and mediating antidepressant responses in the adult brain.
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spelling pubmed-88729882022-03-15 Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity Winkel, Frederike Ryazantseva, Maria Voigt, Mathias B. Didio, Giuliano Lilja, Antonia Llach Pou, Maria Steinzeig, Anna Harkki, Juliana Englund, Jonas Khirug, Stanislav Rivera, Claudio Palva, Satu Taira, Tomi Lauri, Sari E. Umemori, Juzoh Castrén, Eero Mol Psychiatry Article Elevated states of brain plasticity typical for critical periods of early postnatal life can be reinstated in the adult brain through interventions, such as antidepressant treatment and environmental enrichment, and induced plasticity may be critical for the antidepressant action. Parvalbumin-positive (PV) interneurons regulate the closure of developmental critical periods and can alternate between high and low plasticity states in response to experience in adulthood. We now show that PV plasticity states and cortical networks are regulated through the activation of TrkB neurotrophin receptors. Visual cortical plasticity induced by fluoxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant, was lost in mice with reduced expression of TrkB in PV interneurons. Conversely, optogenetic gain-of-function studies revealed that activation of an optically activatable TrkB (optoTrkB) specifically in PV interneurons switches adult cortical networks into a state of elevated plasticity within minutes by decreasing the intrinsic excitability of PV interneurons, recapitulating the effects of fluoxetine. TrkB activation shifted cortical networks towards a low PV configuration, promoting oscillatory synchrony, increased excitatory-inhibitory balance, and ocular dominance plasticity. OptoTrkB activation promotes the phosphorylation of Kv3.1 channels and reduces the expression of Kv3.2 mRNA providing a mechanism for the lower excitability. In addition, decreased expression and puncta of Synaptotagmin2 (Syt2), a presynaptic marker of PV interneurons involved in Ca(2+)-dependent neurotransmitter release, suggests lower inputs onto pyramidal neurons suppressing feed-forward inhibition. Together, the results provide mechanistic insights into how TrkB activation in PV interneurons orchestrates the activity of cortical networks and mediating antidepressant responses in the adult brain. Nature Publishing Group UK 2021-07-28 2021 /pmc/articles/PMC8872988/ /pubmed/34321594 http://dx.doi.org/10.1038/s41380-021-01211-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Winkel, Frederike
Ryazantseva, Maria
Voigt, Mathias B.
Didio, Giuliano
Lilja, Antonia
Llach Pou, Maria
Steinzeig, Anna
Harkki, Juliana
Englund, Jonas
Khirug, Stanislav
Rivera, Claudio
Palva, Satu
Taira, Tomi
Lauri, Sari E.
Umemori, Juzoh
Castrén, Eero
Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity
title Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity
title_full Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity
title_fullStr Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity
title_full_unstemmed Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity
title_short Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity
title_sort pharmacological and optical activation of trkb in parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872988/
https://www.ncbi.nlm.nih.gov/pubmed/34321594
http://dx.doi.org/10.1038/s41380-021-01211-0
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