% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Lange:141303,
author = {Lange, Maren D and Jüngling, Kay and Paulukat, Linda and
Vieler, Marc and Gaburro, Stefano and Sosulina, Liudmila and
Blaesse, Peter and Sreepathi, Hari K and Ferraguti,
Francesco and Pape, Hans-Christian},
title = {{G}lutamic acid decarboxylase 65: a link between
{GABA}ergic synaptic plasticity in the lateral amygdala and
conditioned fear generalization.},
journal = {Neuropsychopharmacology},
volume = {39},
number = {9},
issn = {0893-133X},
address = {Basingstoke},
publisher = {Nature Publishing Group71819},
reportid = {DZNE-2020-07625},
pages = {2211-2220},
year = {2014},
abstract = {An imbalance of the gamma-aminobutyric acid (GABA) system
is considered a major neurobiological pathomechanism of
anxiety, and the amygdala is a key brain region involved.
Reduced GABA levels have been found in anxiety patients, and
genetic variations of glutamic acid decarboxylase (GAD), the
rate-limiting enzyme of GABA synthesis, have been associated
with anxiety phenotypes in both humans and mice. These
findings prompted us to hypothesize that a deficiency of
GAD65, the GAD isoform controlling the availability of GABA
as a transmitter, affects synaptic transmission and
plasticity in the lateral amygdala (LA), and thereby
interferes with fear responsiveness. Results indicate that
genetically determined GAD65 deficiency in mice is
associated with (1) increased synaptic length and release at
GABAergic connections, (2) impaired efficacy of GABAergic
synaptic transmission and plasticity, and (3) reduced
spillover of GABA to presynaptic GABAB receptors, resulting
in a loss of the associative nature of long-term synaptic
plasticity at cortical inputs to LA principal neurons. (4)
In addition, training with high shock intensities in
wild-type mice mimicked the phenotype of GAD65 deficiency at
both the behavioral and synaptic level, indicated by
generalization of conditioned fear and a loss of the
associative nature of synaptic plasticity in the LA. In
conclusion, GAD65 is required for efficient GABAergic
synaptic transmission and plasticity, and for maintaining
extracellular GABA at a level needed for associative
plasticity at cortical inputs in the LA, which, if
disturbed, results in an impairment of the cue specificity
of conditioned fear responses typifying anxiety disorders.},
keywords = {Amygdala: cytology / Amygdala: enzymology / Animals /
Association Learning: physiology / Conditioning,
Psychological: physiology / Electroshock / Extracellular
Space: metabolism / Fear: physiology / Generalization,
Psychological: physiology / Glutamate Decarboxylase:
genetics / Glutamate Decarboxylase: metabolism / Glutamic
Acid: metabolism / Interneurons: cytology / Interneurons:
physiology / Long-Term Potentiation: physiology / Male /
Mice, Inbred C57BL / Mice, Knockout / Neurons: cytology /
Neurons: physiology / Receptors, GABA-B: metabolism /
Synaptic Transmission: physiology / gamma-Aminobutyric Acid:
metabolism / Receptors, GABA-B (NLM Chemicals) / Glutamic
Acid (NLM Chemicals) / gamma-Aminobutyric Acid (NLM
Chemicals) / Glutamate Decarboxylase (NLM Chemicals) /
glutamate decarboxylase 2 (NLM Chemicals)},
cin = {AG Remy},
ddc = {610},
cid = {I:(DE-2719)1013006},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24663011},
pmc = {pmc:PMC4104340},
doi = {10.1038/npp.2014.72},
url = {https://pub.dzne.de/record/141303},
}