PMID- 24211452
OWN - NLM
STAT- MEDLINE
DCOM- 20140804
LR  - 20220309
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Print)
IS  - 0166-4328 (Linking)
VI  - 259
DP  - 2014 Feb 1
TI  - Prefrontal cognitive deficits in mice with altered cerebral cortical GABAergic 
      interneurons.
PG  - 143-51
LID - S0166-4328(13)00676-1 [pii]
LID - 10.1016/j.bbr.2013.10.051 [doi]
AB  - Alterations of inhibitory GABAergic neurons are implicated in multiple 
      psychiatric and neurological disorders, including schizophrenia, autism and 
      epilepsy. In particular, interneuron deficits in prefrontal areas, along with 
      presumed decreased inhibition, have been reported in several human patients. The 
      majority of forebrain GABAergic interneurons arise from a single subcortical 
      source before migrating to their final regional destination. Factors that govern 
      the interneuron populations have been identified, demonstrating that a single 
      gene mutation may globally affect forebrain structures or a single area. In 
      particular, mice lacking the urokinase plasminogen activator receptor (Plaur) 
      gene have decreased GABAergic interneurons in frontal and parietal, but not 
      caudal, cortical regions. Plaur assists in the activation of hepatocyte growth 
      factor/scatter factor (HGF/SF), and several of the interneuron deficits are 
      correlated with decreased levels of HGF/SF. In some cortical regions, the 
      interneuron deficit can be remediated by endogenous overexpression of HGF/SF. In 
      this study, we demonstrate decreased parvalbumin-expressing interneurons in the 
      medial frontal cortex, but not in the hippocampus or basal lateral amygdala in 
      the Plaur null mouse. The Plaur null mouse demonstrates impaired medial frontal 
      cortical function in extinction of cued fear conditioning and the inability to 
      form attentional sets. Endogenous HGF/SF overexpression increased the number of 
      PV-expressing cells in medial frontal cortical areas to levels greater than found 
      in wildtype mice, but did not remediate the behavioral deficits. These data 
      suggest that proper medial frontal cortical function is dependent upon optimum 
      levels of inhibition and that a deficit or excess of interneuron numbers impairs 
      normal cognition.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Bissonette, Gregory B
AU  - Bissonette GB
AD  - Program in Neuroscience, University of Maryland, Baltimore, Baltimore, MD 21201, 
      USA.
FAU - Bae, Mihyun H
AU  - Bae MH
AD  - Department of Anatomy and Neurobiology, University of Maryland School of 
      Medicine, Baltimore, MD 21201, USA.
FAU - Suresh, Tejas
AU  - Suresh T
AD  - Department of Anatomy and Neurobiology, University of Maryland School of 
      Medicine, Baltimore, MD 21201, USA.
FAU - Jaffe, David E
AU  - Jaffe DE
AD  - Department of Anatomy and Neurobiology, University of Maryland School of 
      Medicine, Baltimore, MD 21201, USA.
FAU - Powell, Elizabeth M
AU  - Powell EM
AD  - Program in Neuroscience, University of Maryland, Baltimore, Baltimore, MD 21201, 
      USA; Department of Anatomy and Neurobiology, University of Maryland School of 
      Medicine, Baltimore, MD 21201, USA; Department of Psychiatry, University of 
      Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: 
      epowe001@umaryland.edu.
LA  - eng
GR  - R01 GM057689/GM/NIGMS NIH HHS/United States
GR  - R01 HD067135/HD/NICHD NIH HHS/United States
GR  - R01DA018826/DA/NIDA NIH HHS/United States
GR  - R01 MH57689/MH/NIMH NIH HHS/United States
GR  - R01 MH057683/MH/NIMH NIH HHS/United States
GR  - R01 DA018826/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131107
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Parvalbumins)
RN  - 0 (Plaur protein, mouse)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Attention/physiology
MH  - Cognition Disorders/genetics/*pathology
MH  - GABAergic Neurons/*metabolism
MH  - Gene Expression Regulation/genetics
MH  - Genotype
MH  - Glial Fibrillary Acidic Protein/genetics/metabolism
MH  - Hepatocyte Growth Factor/genetics/metabolism
MH  - Interneurons
MH  - Maze Learning/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Parvalbumins/metabolism
MH  - Prefrontal Cortex/*pathology
MH  - Receptors, Urokinase Plasminogen Activator/genetics/metabolism
PMC - PMC3874795
MID - NIHMS538735
OTO - NOTNLM
OT  - Attentional set
OT  - Cued extinction
OT  - EDS
OT  - GABA
OT  - HGF
OT  - HGF/SF
OT  - IDS
OT  - ID-ED
OT  - ID-ED shift
OT  - MFC
OT  - Morris water maze
OT  - OFC
OT  - PCR
OT  - PV
OT  - Plaur
OT  - SEM
OT  - Urokinase plasminogen activator receptor
OT  - extradimensional shift
OT  - gamma-aminobutyric acid
OT  - gene for hepatocyte growth factor/scatter factor
OT  - gene that encodes urokinase plasminogen activator receptor
OT  - hepatocyte growth factor/scatter factor
OT  - intradimensional shift
OT  - intradimensional-extradimensional (shift)
OT  - medial frontal cortex
OT  - orbital frontal cortex
OT  - parvalbumin
OT  - polymerase chain reaction
OT  - standard error of the mean
EDAT- 2013/11/12 06:00
MHDA- 2014/08/05 06:00
PMCR- 2015/02/01
CRDT- 2013/11/12 06:00
PHST- 2013/06/12 00:00 [received]
PHST- 2013/10/25 00:00 [revised]
PHST- 2013/10/30 00:00 [accepted]
PHST- 2013/11/12 06:00 [entrez]
PHST- 2013/11/12 06:00 [pubmed]
PHST- 2014/08/05 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - S0166-4328(13)00676-1 [pii]
AID - 10.1016/j.bbr.2013.10.051 [doi]
PST - ppublish
SO  - Behav Brain Res. 2014 Feb 1;259:143-51. doi: 10.1016/j.bbr.2013.10.051. Epub 2013 
      Nov 7.