---
_id: '9642'
abstract:
- lang: eng
  text: Perineuronal nets (PNNs), components of the extracellular matrix, preferentially
    coat parvalbumin-positive interneurons and constrain critical-period plasticity
    in the adult cerebral cortex. Current strategies to remove PNN are long-lasting,
    invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic
    ketamine as a method with minimal behavioral effect. We find that this paradigm
    strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like
    plasticity. Microglia are critically involved in PNN loss because they engage
    with parvalbumin-positive neurons in their defined cortical layer. We identify
    external 60-Hz light-flickering entrainment to recapitulate microglia-mediated
    PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques,
    does not induce PNN loss, suggesting microglia might functionally tune to distinct
    brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative
    form of PNN intervention in the healthy adult brain.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank the scientific service units at IST Austria, especially
  the IST bioimaging facility, the preclinical facility, and, specifically, Michael
  Schunn and Sonja Haslinger for excellent support; Plexxikon for the PLX food; the
  Csicsvari group for advice and equipment for in vivo recording; Jürgen Siegert for
  the light-entrainment design; Marco Benevento, Soledad Gonzalo Cogno, Pat King,
  and all Siegert group members for constant feedback on the project and manuscript;
  Lorena Pantano (PILM Bioinformatics Core) for assisting with sample-size determination
  for OD plasticity experiments; and Ana Morello from MIT for technical assistance
  with VEPs recordings. This research was supported by a DOC Fellowship from the Austrian
  Academy of Sciences at the Institute of Science and Technology Austria to R.S.,
  from the European Union Horizon 2020 research and innovation program under the Marie
  Skłodowska-Curie Actions program (grants 665385 to G.C.; 754411 to R.J.A.C.), the
  European Research Council (grant 715571 to S.S.), and the National Eye Institute
  of the National Institutes of Health under award numbers R01EY029245 (to M.F.B.)
  and R01EY023037 (diversity supplement to H.D.J-C.).
article_number: '109313'
article_processing_charge: No
article_type: original
author:
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Rouven
  full_name: Schulz, Rouven
  id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
  last_name: Schulz
  orcid: 0000-0001-5297-733X
- first_name: Héctor
  full_name: De Jesús-Cortés, Héctor
  last_name: De Jesús-Cortés
- first_name: Margaret E
  full_name: Maes, Margaret E
  id: 3838F452-F248-11E8-B48F-1D18A9856A87
  last_name: Maes
  orcid: 0000-0001-9642-1085
- first_name: Balint
  full_name: Nagy, Balint
  id: 93C65ECC-A6F2-11E9-8DF9-9712E6697425
  last_name: Nagy
- first_name: Francis
  full_name: Reilly-Andújar, Francis
  last_name: Reilly-Andújar
- first_name: Gloria
  full_name: Colombo, Gloria
  id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
  last_name: Colombo
  orcid: 0000-0001-9434-8902
- first_name: Ryan J
  full_name: Cubero, Ryan J
  id: 850B2E12-9CD4-11E9-837F-E719E6697425
  last_name: Cubero
  orcid: 0000-0003-0002-1867
- first_name: Florianne E
  full_name: Schoot Uiterkamp, Florianne E
  id: 3526230C-F248-11E8-B48F-1D18A9856A87
  last_name: Schoot Uiterkamp
- first_name: Mark F.
  full_name: Bear, Mark F.
  last_name: Bear
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
citation:
  ama: Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal
    nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment
    in the healthy brain. <i>Cell Reports</i>. 2021;36(1). doi:<a href="https://doi.org/10.1016/j.celrep.2021.109313">10.1016/j.celrep.2021.109313</a>
  apa: Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar,
    F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly
    upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.
    <i>Cell Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2021.109313">https://doi.org/10.1016/j.celrep.2021.109313</a>
  chicago: Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret
    E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia
    Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure
    or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>. Elsevier,
    2021. <a href="https://doi.org/10.1016/j.celrep.2021.109313">https://doi.org/10.1016/j.celrep.2021.109313</a>.
  ieee: A. Venturino <i>et al.</i>, “Microglia enable mature perineuronal nets disassembly
    upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,”
    <i>Cell Reports</i>, vol. 36, no. 1. Elsevier, 2021.
  ista: Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar
    F, Colombo G, Cubero RJ, Schoot Uiterkamp FE, Bear MF, Siegert S. 2021. Microglia
    enable mature perineuronal nets disassembly upon anesthetic ketamine exposure
    or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313.
  mla: Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly
    upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.”
    <i>Cell Reports</i>, vol. 36, no. 1, 109313, Elsevier, 2021, doi:<a href="https://doi.org/10.1016/j.celrep.2021.109313">10.1016/j.celrep.2021.109313</a>.
  short: A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar,
    G. Colombo, R.J. Cubero, F.E. Schoot Uiterkamp, M.F. Bear, S. Siegert, Cell Reports
    36 (2021).
date_created: 2021-07-11T22:01:16Z
date_published: 2021-07-06T00:00:00Z
date_updated: 2023-08-10T14:09:39Z
day: '06'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.celrep.2021.109313
ec_funded: 1
external_id:
  isi:
  - '000670188500004'
  pmid:
  - '34233180'
file:
- access_level: open_access
  checksum: f056255f6d01fd9a86b5387635928173
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-07-19T13:32:17Z
  date_updated: 2021-07-19T13:32:17Z
  file_id: '9693'
  file_name: 2021_CellReports_Venturino.pdf
  file_size: 56388540
  relation: main_file
  success: 1
file_date_updated: 2021-07-19T13:32:17Z
has_accepted_license: '1'
intvolume: '        36'
isi: 1
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715571'
  name: Microglia action towards neuronal circuit formation and function in health
    and disease
publication: Cell Reports
publication_identifier:
  eissn:
  - '22111247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/the-twinkle-and-the-brain/
scopus_import: '1'
status: public
title: Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine
  exposure or 60-Hz light entrainment in the healthy brain
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 36
year: '2021'
...
