Document Detail


Cellular correlates of anxiety in CA1 hippocampal pyramidal cells of 5-HT1A receptor knockout mice.
MedLine Citation:
PMID:  20981413     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: 5-HT(1A) receptor knockout (1AKO) mice have a robust anxiety phenotype. Tissue-specific "rescue" strategies and electrophysiology have implicated a critical role for postsynaptic 5-HT(1A) receptors, particularly in the CA1 region of the hippocampus.
OBJECTIVES: In this study, we evaluated differences in membrane properties and synaptic activity in CA1 hippocampal pyramidal cells between 1AKOs and wild-type (WT) controls to better understand the cellular correlates of anxiety in this mouse model.
METHODS: Whole-cell patch-clamp recordings were conducted in CA1 pyramidal cells in hippocampal brain slices from 1AKOs and WTs that had previously been screened for anxiety with the elevated-plus maze. Spontaneous miniature inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs) and stimulus-evoked eIPSCs and eEPSCs were recorded in addition to the effect of the benzodiazepine agonist diazepam or the inverse agonist FG 7142 on γ-aminobutyric acid (GABA)ergic eIPSCs.
RESULTS: Evoked EPSC amplitude was greater in 1AKOs than WTs. When subjects were pooled across genotypes, anxiety measures correlated with eEPSC amplitude, indicating enhanced postsynaptic glutamate synaptic activity under conditions of synaptic activation in anxious subjects. While GABA synaptic activity and sensitivity to diazepam were not affected by genotype or correlated with anxiety, sensitivity to the anxiogenic FG 7142 was smaller in anxious subjects.
CONCLUSIONS: These data indicate enhanced postsynaptic glutamate receptor sensitivity and decreased GABAergic inhibition by a benzodiazepine inverse agonist in CA1 hippocampal neurons of anxious mice are produced by deletion of the 5-HT(1A) receptor. These data provide new information about interactions between 5-HT, GABA, and glutamate systems during the expression of chronic anxiety.
Authors:
Emily Freeman-Daniels; Sheryl G Beck; Lynn G Kirby
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-28
Journal Detail:
Title:  Psychopharmacology     Volume:  213     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-02     Completed Date:  2011-05-24     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  453-63     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Anxiety Agents / pharmacology*
Anxiety / drug therapy,  physiopathology*
Carbolines / pharmacology
Diazepam / pharmacology
Disease Models, Animal
Excitatory Postsynaptic Potentials
Glutamic Acid / metabolism
Inhibitory Postsynaptic Potentials
Male
Maze Learning / drug effects
Mice
Mice, Knockout
Patch-Clamp Techniques
Pyramidal Cells / metabolism*
Receptor, Serotonin, 5-HT1A / genetics,  metabolism*
gamma-Aminobutyric Acid / metabolism
Grant Support
ID/Acronym/Agency:
MH 48125/MH/NIMH NIH HHS; MH 63078/MH/NIMH NIH HHS; MH 63301/MH/NIMH NIH HHS; P01 MH048125/MH/NIMH NIH HHS; R01 MH063078-05/MH/NIMH NIH HHS; R01 MH075047-01A1/MH/NIMH NIH HHS; R21 MH099488/MH/NIMH NIH HHS; RC1 MH089800/MH/NIMH NIH HHS; RC1 MH089800-01/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Anxiety Agents; 0/Carbolines; 112692-38-3/Receptor, Serotonin, 5-HT1A; 439-14-5/Diazepam; 56-12-2/gamma-Aminobutyric Acid; 56-86-0/Glutamic Acid; 78538-74-6/FG 7142
Comments/Corrections

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