PMID- 36990270
OWN - NLM
STAT- MEDLINE
DCOM- 20230523
LR  - 20230602
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 519
DP  - 2023 May 21
TI  - Theta/gamma Co-modulation Disruption After NMDAr Blockade by MK-801 Is Associated 
      with Spatial Working Memory Deficits in Mice.
PG  - 162-176
LID - S0306-4522(23)00145-8 [pii]
LID - 10.1016/j.neuroscience.2023.03.022 [doi]
AB  - Abnormal N-methyl-D-aspartate receptor (NMDAr) function has been linked to 
      oscillopathies, psychosis, and cognitive dysfunction in schizophrenia (SCZ). 
      Here, we investigate the role of NMDAr hypofunction in pathological oscillations 
      and behavior. We implanted mice with tetrodes in the dorsal/intermediate 
      hippocampus and medial prefrontal cortex (mPFC), administered the NMDAr 
      antagonist MK-801, and recorded oscillations during spontaneous exploration in an 
      open field and in the y-maze spatial working memory test. Our results show that 
      NMDAr blockade disrupted the correlation between oscillations and speed of 
      movement, crucial for internal representations of distance. In the hippocampus, 
      MK-801 increased gamma oscillations and disrupted theta/gamma coupling during 
      spatial working memory. In the mPFC, MK-801 increased the power of theta and 
      gamma, generated high-frequency oscillations (HFO 155-185 Hz), and disrupted 
      theta/gamma coupling. Moreover, the performance of mice in the spatial working 
      memory version of the y-maze was strongly correlated with CA1-PFC theta/gamma 
      co-modulation. Thus, theta/gamma mediated by NMDAr function might explain several 
      of SCZ's cognitive symptoms and might be crucial to explaining hippocampal-PFC 
      interaction.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Abad-Perez, P
AU  - Abad-Perez P
AD  - Universidad Cardenal Herrera-CEU, CEU Universities, Spain; Instituto de 
      Neurociencias UMH-CSIC, Alicante, Spain.
FAU - Molina-Paya, F J
AU  - Molina-Paya FJ
AD  - Universidad Cardenal Herrera-CEU, CEU Universities, Spain.
FAU - Martinez-Otero, L
AU  - Martinez-Otero L
AD  - Instituto de Neurociencias UMH-CSIC, Alicante, Spain.
FAU - Borrell, V
AU  - Borrell V
AD  - Instituto de Neurociencias UMH-CSIC, Alicante, Spain.
FAU - Redondo, R L
AU  - Redondo RL
AD  - Roche Pharma Research and Early Development, Neuroscience and Rare Diseases, 
      Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 
      4070 Basel, Switzerland.
FAU - Brotons-Mas, J R
AU  - Brotons-Mas JR
AD  - Universidad Cardenal Herrera-CEU, CEU Universities, Spain; Instituto de 
      Neurociencias UMH-CSIC, Alicante, Spain. Electronic address: 
      Jorge.brotonsmas@chceu.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230328
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Dizocilpine Maleate/pharmacology
MH  - *Memory, Short-Term
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Prefrontal Cortex/metabolism
MH  - Theta Rhythm/physiology
MH  - Hippocampus/metabolism
MH  - Memory Disorders/chemically induced
MH  - Spatial Memory
PMC - PMC10229075
OTO - NOTNLM
OT  - NMDAr
OT  - hippocampus
OT  - oscillatory activity
OT  - prefrontal cortex
OT  - schizophrenia
COIS- 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.
EDAT- 2023/03/30 06:00
MHDA- 2023/05/23 06:42
PMCR- 2023/05/21
CRDT- 2023/03/29 19:32
PHST- 2023/01/26 00:00 [received]
PHST- 2023/03/16 00:00 [revised]
PHST- 2023/03/21 00:00 [accepted]
PHST- 2023/05/23 06:42 [medline]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/29 19:32 [entrez]
PHST- 2023/05/21 00:00 [pmc-release]
AID - S0306-4522(23)00145-8 [pii]
AID - 10.1016/j.neuroscience.2023.03.022 [doi]
PST - ppublish
SO  - Neuroscience. 2023 May 21;519:162-176. doi: 10.1016/j.neuroscience.2023.03.022. 
      Epub 2023 Mar 28.