Volume 11 Supplement 2

17th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Fear learning induces structural and functional plasticity at GABAergic synapses in the basolateral amygdala

  • Yu Kasugai1,
  • Elisabeth Vogel2,
  • Markus Hauschild3,
  • Ramon O Tasan1,
  • Yvan Peterschmitt1, 5,
  • Andreas Lüthi2,
  • Ryuichi Shigemoto4,
  • Werner Sieghart5,
  • Nicolas Singewald3,
  • Günther Sperk1 and
  • Francesco Ferraguti1Email author
BMC Pharmacology201111(Suppl 2):A42

https://doi.org/10.1186/1471-2210-11-S2-A42

Published: 5 September 2011

Background

Previous work has suggested that alterations in GABAergic function within the amygdala underlie fear learning. In particular, it has been shown that Pavlovian fear conditioning induces a downregulation of benzodiazepine binding sites as well as transcripts for gephyrin and some GABAA receptor subunits in the basal nucleus of the amygdala (BA), which were restored to control levels after fear extinction.

Methods

We have undertaken a combined anatomical and physiological approach to examine whether these alterations distinctively involve GABAA receptors in synaptic or extrasynaptic areas. Specifically, we analyzed – in the BA of mice that underwent fear conditioning as well as extinction – miniature inhibitory postsynaptic currents (mIPSCs), mRNA levels by in situ hybridization, and the density for the GABAA γ2 subunit by means of the freeze-fracture replica immunolabelling technique (SDS-FRL). SDS-FRL also allowed to precisely measure the size of GABAergic synapses.

Results

A significant decrease in labelling density for the GABAA γ2 subunit could be detected in the synaptic area in fear-conditioned mice as compared to the control group and mice that had undergone extinction (p < 0.01; Kruskal-Wallis and Dunn’s multiple comparison tests). Conversely, GABAA γ2 extrasynaptic density was lower in the extinction group when compared to both the control and fear-conditioned mice (p < 0.005). The average size of GABAergic synapses in control mice was 0.034 ± 0.001 µm2 (n = 227 full synapses from 3 animals; CV = 0.62). Fear-conditioned animals showed a significantly (p < 0.01) larger average synaptic size (0.040 ± 0.001 µm2; n = 249; CV = 0.59), whereas in fear extinction mice it was similar to controls (0.031 ± 0.001 µm2; n = 290; CV = 0.59). Alterations in synapse size upon fear conditioning and extinction were associated with functional changes. In neurons recorded from acute slices obtained from fear-conditioned animals mIPSCs were larger (increased charge transfer/mIPSC) compared to recordings obtained from slices of control mice and animals subjected to extinction training. In situ hybridization analysis of the mRNA content for GABAA γ2 subunits revealed highly similar levels among the 3 groups in the BA (p = 31, one-way ANOVA) and central nucleus (p = 41).

Conclusions

Our results indicate that, in the BA, fear conditioning produces a reversible enlargement of GABAergic synapses and an increase in mIPSC charge transfer with no change in the overall number of synaptic GABAA receptors.

Declarations

Acknowledgements

This work was supported by the FWF grant S10720 to F.F.

Authors’ Affiliations

(1)
Department of Pharmacology, Innsbruck Medical University
(2)
Friedrich Miescher Institute for Biomedical Research
(3)
Department of Pharmacology and Toxicology, Institute of Pharmacy, and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck
(4)
Division of Cerebral Structure, National Institute for Physiological Sciences
(5)
Department of Biochemistry and Molecular Biology, Center for Brain Research, Medical University of Vienna

Copyright

© Kasugai et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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