Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

NMDAr BLOCKING BY MK801 ALTERS HIPPOCAMPAL AND PREFRONTAL CORTEX OSCILLATIONS AND IMPAIRS SPATIAL WORKING MEMORY IN MICE

P. Abad-Perez, L. Martínez-Otero, View ORCID ProfileV. Borrell, R. Redondo, J.R. Brotons-Mas
doi: https://doi.org/10.1101/2021.09.22.461383
P. Abad-Perez
1Universidad Cardenal Herrera CEU, Elche
2Instituto de Neurociencias UMH-CSIC. Alicante
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. Martínez-Otero
2Instituto de Neurociencias UMH-CSIC. Alicante
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V. Borrell
2Instituto de Neurociencias UMH-CSIC. Alicante
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for V. Borrell
R. Redondo
3Roche Pharma Research and Early Development, Neuroscience and Rare Diseases, Roche Innovation Center Basel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J.R. Brotons-Mas
1Universidad Cardenal Herrera CEU, Elche
2Instituto de Neurociencias UMH-CSIC. Alicante
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Jorge.brotonsmas@chceu.es
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Abnormal NMDAr function has been linked to rhythmopathies, psychosis, and cognitive dysfunction in schizophrenia. Here, we investigate the role of NMDAr hypofunction in pathological oscillations and behavior. We implanted mice with tetrodes in the dorsal hippocampus and medial prefrontal cortex (mPFC) and administered them with the NMDAr antagonist MK801, recording oscillations during spontaneous exploration in an open field and in the y-maze spatial working memory test. Our results show that NMDAr blockade increased locomotor activity and impaired spatial working memory. The administration of MK801 disrupted the correlation between oscillations and speed of movement, crucial for internal representations of distance. In the hippocampus, MK801 impaired gamma oscillations and theta/gamma coupling, while in the mPFC, it increased the power of theta, gamma, and generated high-frequency oscillations (HFO 155-185 Hz). Spatial working memory tests in the y-maze revealed that theta/gamma coupling was consistently higher in correct trials. Theta/gamma co-modulation mediated by NMDAr function might be key to explain various of schizophrenia’s cognitive symptoms. Further investigating NMDAr hypofunction’s role in the emergence of aberrant oscillatory activity will improve our understanding of schizophrenia and inspire new treatments of psychiatric disorders.

Highlights

  • – NMDAr blockade increases motor behavior and impairs spatial working memory.

  • – NMDAr hypofunction differentially alters oscillatory activity in the hippocampus and PFC.

  • – NMDAr blockade generates locally modulated high-frequency oscillations in the PFC.

  • – Theta/gamma modulation, but also long-range theta/gamma modulation across CA1 and the PFC is involved in spatial working memory.

  • – NMDAr blockade disrupts the correlation between theta/gamma co-modulation and spatial working memory performances.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Declaration of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted September 24, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
NMDAr BLOCKING BY MK801 ALTERS HIPPOCAMPAL AND PREFRONTAL CORTEX OSCILLATIONS AND IMPAIRS SPATIAL WORKING MEMORY IN MICE
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
NMDAr BLOCKING BY MK801 ALTERS HIPPOCAMPAL AND PREFRONTAL CORTEX OSCILLATIONS AND IMPAIRS SPATIAL WORKING MEMORY IN MICE
P. Abad-Perez, L. Martínez-Otero, V. Borrell, R. Redondo, J.R. Brotons-Mas
bioRxiv 2021.09.22.461383; doi: https://doi.org/10.1101/2021.09.22.461383
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
NMDAr BLOCKING BY MK801 ALTERS HIPPOCAMPAL AND PREFRONTAL CORTEX OSCILLATIONS AND IMPAIRS SPATIAL WORKING MEMORY IN MICE
P. Abad-Perez, L. Martínez-Otero, V. Borrell, R. Redondo, J.R. Brotons-Mas
bioRxiv 2021.09.22.461383; doi: https://doi.org/10.1101/2021.09.22.461383

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (3512)
  • Biochemistry (7352)
  • Bioengineering (5329)
  • Bioinformatics (20277)
  • Biophysics (10026)
  • Cancer Biology (7749)
  • Cell Biology (11319)
  • Clinical Trials (138)
  • Developmental Biology (6440)
  • Ecology (9958)
  • Epidemiology (2065)
  • Evolutionary Biology (13336)
  • Genetics (9362)
  • Genomics (12592)
  • Immunology (7714)
  • Microbiology (19046)
  • Molecular Biology (7447)
  • Neuroscience (41063)
  • Paleontology (300)
  • Pathology (1231)
  • Pharmacology and Toxicology (2139)
  • Physiology (3164)
  • Plant Biology (6866)
  • Scientific Communication and Education (1274)
  • Synthetic Biology (1898)
  • Systems Biology (5318)
  • Zoology (1089)