PMID- 26042007
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150604
LR  - 20201001
IS  - 1662-5153 (Print)
IS  - 1662-5153 (Electronic)
IS  - 1662-5153 (Linking)
VI  - 9
DP  - 2015
TI  - Altered neuronal excitability underlies impaired hippocampal function in an 
      animal model of psychosis.
PG  - 117
LID - 10.3389/fnbeh.2015.00117 [doi]
LID - 117
AB  - Psychosis is accompanied by severe attentional deficits, and impairments in 
      associational-memory processing and sensory information processing that are 
      ascribed to dysfunctions in prefrontal and hippocampal function. Disruptions of 
      glutamatergic signaling may underlie these alterations: Antagonism of the 
      N-methyl-D-aspartate receptor (NMDAR) results in similar molecular, cellular, 
      cognitive and behavioral changes in rodents and/or humans as those that occur in 
      psychosis, raising the question as to whether changes in glutamatergic 
      transmission may be intrinsic to the pathophysiology of the disease. In an animal 
      model of psychosis that comprises treatment with the irreversible 
      NMDAR-antagonist, MK801, we explored the cellular mechanisms that may underlie 
      hippocampal dysfunction in psychosis. MK801-treatment resulted in a profound loss 
      of hippocampal LTP that was evident 4 weeks after treatment. Whereas neuronal 
      expression of the immediate early gene, Arc, was enhanced in the hippocampus by 
      spatial learning in controls, MK801-treated animals failed to show 
      activity-dependent increases in Arc expression. By contrast, a significant 
      increase in basal Arc expression in the absence of learning was evident compared 
      to controls. Paired-pulse (PP) facilitation was increased at the 40 ms interval 
      indicating that NMDAR and/or fast GABAergic-mediated neurotransmission was 
      disrupted. In line with this, MK801-treatment resulted in a significant decrease 
      in GABA(A), and increase in GABA(B)-receptor-expression in PFC, along with a 
      significant increase of GABA(B)- and NMDAR-GluN2B expression in the dentate 
      gyrus. NMDAR-GluN1 or GluN2A subunit expression was unchanged. These data suggest 
      that in psychosis, deficits in hippocampus-dependent memory may be caused by a 
      loss of hippocampal LTP that arises through enhanced hippocampal neuronal 
      excitability, altered GluN2B and GABA receptor expression and an uncoupling of 
      the hippocampus-prefrontal cortex circuitry.
FAU - Gruter, Thomas
AU  - Gruter T
AD  - Medical Faculty, Department of Neurophysiology, Ruhr University Bochum Bochum, 
      Germany ; International Graduate School of Neuroscience, Ruhr University Bochum 
      Bochum, Germany.
FAU - Wiescholleck, Valentina
AU  - Wiescholleck V
AD  - Medical Faculty, Department of Neurophysiology, Ruhr University Bochum Bochum, 
      Germany.
FAU - Dubovyk, Valentyna
AU  - Dubovyk V
AD  - Medical Faculty, Department of Neurophysiology, Ruhr University Bochum Bochum, 
      Germany.
FAU - Aliane, Verena
AU  - Aliane V
AD  - Medical Faculty, Department of Neurophysiology, Ruhr University Bochum Bochum, 
      Germany.
FAU - Manahan-Vaughan, Denise
AU  - Manahan-Vaughan D
AD  - Medical Faculty, Department of Neurophysiology, Ruhr University Bochum Bochum, 
      Germany ; International Graduate School of Neuroscience, Ruhr University Bochum 
      Bochum, Germany.
LA  - eng
PT  - Journal Article
DEP - 20150520
PL  - Switzerland
TA  - Front Behav Neurosci
JT  - Frontiers in behavioral neuroscience
JID - 101477952
PMC - PMC4438226
OTO - NOTNLM
OT  - GABA
OT  - MK801
OT  - NMDA receptor hypofunction
OT  - hippocampus
OT  - in vivo
OT  - schizophrenia
EDAT- 2015/06/05 06:00
MHDA- 2015/06/05 06:01
PMCR- 2015/01/01
CRDT- 2015/06/05 06:00
PHST- 2015/01/13 00:00 [received]
PHST- 2015/04/22 00:00 [accepted]
PHST- 2015/06/05 06:00 [entrez]
PHST- 2015/06/05 06:00 [pubmed]
PHST- 2015/06/05 06:01 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 10.3389/fnbeh.2015.00117 [doi]
PST - epublish
SO  - Front Behav Neurosci. 2015 May 20;9:117. doi: 10.3389/fnbeh.2015.00117. 
      eCollection 2015.