PMID- 33112474
OWN - NLM
STAT- MEDLINE
DCOM- 20211125
LR  - 20221005
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Print)
IS  - 1050-9631 (Linking)
VI  - 30
IP  - 12
DP  - 2020 Dec
TI  - NMDA receptors promote hippocampal sharp-wave ripples and the associated 
      coactivity of CA1 pyramidal cells.
PG  - 1356-1370
LID - 10.1002/hipo.23276 [doi]
AB  - Hippocampal sharp-wave ripples (SWRs) support the reactivation of memory 
      representations, relaying information to neocortex during "offline" and 
      sleep-dependent memory consolidation. While blockade of NMDA receptors (NMDAR) is 
      known to affect both learning and subsequent consolidation, the specific 
      contributions of NMDAR activation to SWR-associated activity remain unclear. 
      Here, we combine biophysical modeling with in vivo local field potential (LFP) 
      and unit recording to quantify changes in SWR dynamics following inactivation of 
      NMDAR. In a biophysical model of CA3-CA1 SWR activity, we find that NMDAR removal 
      leads to reduced SWR density, but spares SWR properties such as duration, cell 
      recruitment and ripple frequency. These predictions are confirmed by experiments 
      in which NMDAR-mediated transmission in rats was inhibited using three different 
      NMDAR antagonists, while recording dorsal CA1 LFP. In the model, loss of 
      NMDAR-mediated conductances also induced a reduction in the proportion of cell 
      pairs that co-activate significantly above chance across multiple events. Again, 
      this prediction is corroborated by dorsal CA1 single-unit recordings, where the 
      NMDAR blocker ketamine disrupted correlated spiking during SWR. Our results are 
      consistent with a framework in which NMDA receptors both promote activation of 
      SWR events and organize SWR-associated spiking content. This suggests that, while 
      SWR are short-lived events emerging in fast excitatory-inhibitory networks, 
      slower network components including NMDAR-mediated currents contribute to ripple 
      density and promote consistency in the spiking content across ripples, 
      underpinning mechanisms for fine-tuning of memory consolidation processes.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Howe, Timothy
AU  - Howe T
AD  - School of Physiology, Pharmacology and Neuroscience, University of Bristol, 
      Bristol, UK.
FAU - Blockeel, Anthony J
AU  - Blockeel AJ
AD  - School of Physiology, Pharmacology and Neuroscience, University of Bristol, 
      Bristol, UK.
FAU - Taylor, Hannah
AU  - Taylor H
AD  - School of Physiology, Pharmacology and Neuroscience, University of Bristol, 
      Bristol, UK.
FAU - Jones, Matthew W
AU  - Jones MW
AD  - School of Physiology, Pharmacology and Neuroscience, University of Bristol, 
      Bristol, UK.
FAU - Bazhenov, Maxim
AU  - Bazhenov M
AD  - Department of Medicine, University of California San Diego, La Jolla, California, 
      USA.
FAU - Malerba, Paola
AU  - Malerba P
AUID- ORCID: 0000-0002-8733-899X
AD  - School of Physiology, Pharmacology and Neuroscience, University of Bristol, 
      Bristol, UK.
AD  - Battelle Center for Mathematical Medicine, Columbus, Ohio, USA.
LA  - eng
GR  - RF1 MH117155/MH/NIMH NIH HHS/United States
GR  - G0501146/MRC_/Medical Research Council/United Kingdom
GR  - R01 MH125557/MH/NIMH NIH HHS/United States
GR  - R01 NS109553/NS/NINDS NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - RF1MH117155/National Institute of Health/
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20201028
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Animals
MH  - CA1 Region, Hippocampal/cytology/drug effects/*physiology
MH  - Electrodes, Implanted
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - *Models, Neurological
MH  - Pyramidal Cells/drug effects/*physiology
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology
PMC - PMC8645203
MID - NIHMS1740852
OTO - NOTNLM
OT  - NMDA receptors
OT  - computational model
OT  - sharp-wave ripples
OT  - spindles
COIS- CONFLICT OF INTEREST The authors declare no conflict of interest.
EDAT- 2020/10/29 06:00
MHDA- 2021/11/26 06:00
PMCR- 2021/12/05
CRDT- 2020/10/28 12:12
PHST- 2019/10/22 00:00 [received]
PHST- 2020/10/05 00:00 [revised]
PHST- 2020/10/15 00:00 [accepted]
PHST- 2020/10/29 06:00 [pubmed]
PHST- 2021/11/26 06:00 [medline]
PHST- 2020/10/28 12:12 [entrez]
PHST- 2021/12/05 00:00 [pmc-release]
AID - 10.1002/hipo.23276 [doi]
PST - ppublish
SO  - Hippocampus. 2020 Dec;30(12):1356-1370. doi: 10.1002/hipo.23276. Epub 2020 Oct 
      28.