PMID- 29861281
OWN - NLM
STAT- MEDLINE
DCOM- 20190805
LR  - 20190805
IS  - 1097-4199 (Electronic)
IS  - 0896-6273 (Print)
IS  - 0896-6273 (Linking)
VI  - 98
IP  - 6
DP  - 2018 Jun 27
TI  - Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: 
      Implications for Activity-Dependent Disconnection in Schizophrenia.
PG  - 1243-1255.e5
LID - S0896-6273(18)30382-9 [pii]
LID - 10.1016/j.neuron.2018.05.010 [doi]
AB  - We employed multi-electrode array recording to evaluate the influence of NMDA 
      receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as 
      they performed a cognitive control task measuring specific deficits in 
      schizophrenia. Systemic, periodic administration of an NMDAR antagonist 
      (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike 
      correlation in simultaneously recorded neuron pairs. We employed transfer entropy 
      analysis to measure effective connectivity between prefrontal neurons at lags 
      consistent with monosynaptic interactions and found that effective connectivity 
      was persistently reduced following exposure to the NMDAR antagonist. These 
      results suggest that a disruption of spike timing and effective connectivity 
      might be interrelated factors in pathogenesis, supporting an activity-dependent 
      disconnection theory of schizophrenia. In this theory, disruption of NMDAR 
      synaptic function leads to dysregulated timing of action potentials in prefrontal 
      networks, accelerating synaptic disconnection through a spike-timing-dependent 
      mechanism.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Zick, Jennifer L
AU  - Zick JL
AD  - Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; 
      Medical Scientist Training Program (MD/PhD), University of Minnesota, 
      Minneapolis, MN 55455, USA.
FAU - Blackman, Rachael K
AU  - Blackman RK
AD  - Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; 
      Medical Scientist Training Program (MD/PhD), University of Minnesota, 
      Minneapolis, MN 55455, USA.
FAU - Crowe, David A
AU  - Crowe DA
AD  - Department of Biology, Augsburg University, Minneapolis, MN 55454, USA.
FAU - Amirikian, Bagrat
AU  - Amirikian B
AD  - Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; 
      Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, 
      USA; Brain Sciences Center, VA Medical Center, Minneapolis, MN 55417, USA.
FAU - DeNicola, Adele L
AU  - DeNicola AL
AD  - Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; 
      Brain Sciences Center, VA Medical Center, Minneapolis, MN 55417, USA.
FAU - Netoff, Theoden I
AU  - Netoff TI
AD  - Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, 
      55455 USA.
FAU - Chafee, Matthew V
AU  - Chafee MV
AD  - Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; 
      Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, 
      USA; Brain Sciences Center, VA Medical Center, Minneapolis, MN 55417, USA. 
      Electronic address: chafe001@umn.edu.
LA  - eng
GR  - R25 MH101076/MH/NIMH NIH HHS/United States
GR  - F31 MH109238/MH/NIMH NIH HHS/United States
GR  - F30 MH108205/MH/NIMH NIH HHS/United States
GR  - R01 MH077779/MH/NIMH NIH HHS/United States
GR  - R01 MH107491/MH/NIMH NIH HHS/United States
GR  - T32 GM008471/GM/NIGMS NIH HHS/United States
GR  - T32 GM008244/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180531
PL  - United States
TA  - Neuron
JT  - Neuron
JID - 8809320
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - J1DOI7UV76 (Phencyclidine)
MH  - Action Potentials/drug effects/physiology
MH  - Animals
MH  - Cognition/drug effects/*physiology
MH  - Cortical Synchronization/drug effects/*physiology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Executive Function/drug effects/*physiology
MH  - Macaca mulatta
MH  - Neural Pathways/drug effects/metabolism/physiopathology
MH  - Neurons/drug effects/*metabolism
MH  - Phencyclidine/pharmacology
MH  - Prefrontal Cortex/drug effects/*metabolism/physiopathology
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism
MH  - Schizophrenia/*metabolism/physiopathology
MH  - Task Performance and Analysis
MH  - Time Factors
PMC - PMC6085178
MID - NIHMS981962
OTO - NOTNLM
OT  - NMDAR antagonist
OT  - STDP
OT  - animal model
OT  - cross correlation
OT  - effective connectivity
OT  - neural synchrony
OT  - nonhuman primate
OT  - spike correlation
OT  - transfer entropy
EDAT- 2018/06/05 06:00
MHDA- 2019/08/06 06:00
PMCR- 2018/08/09
CRDT- 2018/06/05 06:00
PHST- 2017/10/01 00:00 [received]
PHST- 2018/03/06 00:00 [revised]
PHST- 2018/05/04 00:00 [accepted]
PHST- 2018/06/05 06:00 [pubmed]
PHST- 2019/08/06 06:00 [medline]
PHST- 2018/06/05 06:00 [entrez]
PHST- 2018/08/09 00:00 [pmc-release]
AID - S0896-6273(18)30382-9 [pii]
AID - 10.1016/j.neuron.2018.05.010 [doi]
PST - ppublish
SO  - Neuron. 2018 Jun 27;98(6):1243-1255.e5. doi: 10.1016/j.neuron.2018.05.010. Epub 
      2018 May 31.