| Abstract No.: | A-B1066 |
| Country: | Germany |
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| Title: | EXPRESSION OF GABA-RELATED GENES IN THE AMYGDALA, HIPPOCAMPUS, AND PREFRONTAL CORTEX AFTER EXTINCTION OF FEAR |
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| Authors/Affiliations: | 1 Susan Sangha*; 1 Hans-Christian Pape;
1 Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-Universitaet Muenster, Germany
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| Content: | BACKGROUND: Extinction is demonstrated as a reduction in fear that occurs when stimuli once associated with an aversive event are no longer coupled with that event and involves new learning and memory formation rather than erasure of the original memory. This approach to reducing fear forms the basis of most behavioural therapies in treating anxiety disorders such as phobias and Post-traumatic Stress Disorder. Previous data from our laboratory have already demonstrated changes in theta synchrony patterns between the amygdala, hippocampus and prefrontal cortex after extinction of auditory fear conditioning. Pharmacological studies have also implicated GABA in extinction learning. In addition, transgenic mouse studies from our laboratory indicate that the GABA synthesizing enzyme GAD65 is required for extinction.
OBJECTIVE: Changes in gene expression of the GABA synthesizing enzymes GAD67 and GAD65, the GABA(A) receptor subunits alpha1, alpha2, and alpha3, and the GABA receptor clustering proteins profilin and gephyrin were investigated in the amygdala, hippocampus and prefrontal cortex.
MATERIALS & METHODS: C57/BL6 mice underwent either fear conditioning training alone (FC) or fear conditioning followed by extinction training (FC+E). Control animals received either unpaired conditioning alone (UC) or unpaired conditioning followed by extinction training (UC+E). Brains were isolated between 24-26 hours after training. Individual substructures of the hippocampus (dentate gyrus, CA1), amygdala (lateral nucleus, basolateral nucleus, central nucleus) and the prefrontal cortex (infralimbic, prelimbic) were isolated via laser micro-dissection. After the isolation of RNA, relative quantitative real-time RT-PCR was performed. Threshold cycle values were normalized to a housekeeping gene (PGK) for each gene of interest. These values for each of the 4 conditioned groups were again normalized to naïve controls.
RESULTS: Thus far, the major effects appear to be in the dentate gyrus and the central amygdala. Specifically, in the dentate gyrus, an increase in the GABA(A)R-alpha3 subunit was observed for the UC and FC+E groups. In the central amygdala, FC resulted in increased GABA(A)R-alpha2 subunit RNA levels. More interestingly, RNA levels for all genes of interest were increased in the central amygdala in the FC+E group when compared to the UC+E. CONCLUSION: These preliminary data suggest that the central amygdala may be involved in the long-term regulation of GABA-related genes after the extinction of fear.
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