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Open Access

Establishing a new mouse model for investigating the function of amygdala neurons in anxiety

  • Yvan Peterschmitt1, 2,
  • Stefan Weger3,
  • Alexander Plauth3,
  • Regine Heilbronn3,
  • William Wisden4,
  • Günther Sperk1 and
  • Werner Sieghart2Email author
BMC Pharmacology20088(Suppl 1):A35

https://doi.org/10.1186/1471-2210-8-S1-A35

Published: 5 November 2008

Benzodiazepine site agonists modulate the firing pattern of neurons via GABAA receptors and by that influence the activity of the network in which they participate and cause appropriate changes in behaviour. Since the amygdala is involved in regulating anxiety, it can be expected that GABAA receptors located in this brain region contribute to the anxiolytic effects of benzodiazepine site agonists. Here we take advantage of an in vivo mouse model [1] in which a Phe to Ile point mutation was introduced into the gene coding for the GABAA receptor γ2 subunit. This γ2F77I mutation, which was also flanked by loxP sites, affects only the benzodiazepine binding site of the respective receptors, and mice carrying this mutation no longer are sensitive to certain benzodiazepine site agonists but are otherwise normal. Here we aim to selectively replace the "benzodiazepine insensitive" mutated γ2F77I subunit by a GFP-labeled native one in the amygdala of γ2F77Ilox mice by a stereotaxic injection of recombinant adeno-associated viral (rAAV) vectors expressing Cre-recombinase and GFP-labeled wild-type γ2 subunits. It has been demonstrated previously that the replaced wild-type subunits combine with endogenous subunits to form completely assembled receptors with normal subcellular distribution. Then only those amygdala neurons expressing the GFP-labeled wild-type γ2 subunits can be modulated by a systemic application of these benzodiazepine site agonists and any behavioural effects observed with these drugs must have been generated via these neurons. In this report we present a preliminary characterization of the newly developed mouse model demonstrating the correct expression of Cre-recombinase and GFP-labeled wild-type γ2 subunits in amygdala neurons by immunohistochemical and in situ hybridization techniques. Future experiments aim to characterize our model by behavioural pharmacology in paradigms of anxiety.

Declarations

Acknowledgements

Financial support by the NFN-project S10203-B13 of the Austrian Science Fund is gratefully acknowledged.

Authors’ Affiliations

(1)
Institute of Pharmacology, Medical University of Innsbruck
(2)
Center for Brain Research, Medical University of Vienna
(3)
Institute of Virology, Charité Centrum, Medical University of Berlin
(4)
Institute of Medical Sciences, University of Aberdeen

References

  1. Wulff P, Goetz T, Leppä E, Linden AM, Renzi M, Swinny JD, Vekovischeva OY, Sieghart W, Somogyi P, Korpi ER, Farrant M, Wisden W: From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Nature Neurosci. 2007, 10: 923-929. 10.1038/nn1927.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Peterschmitt et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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