کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4180934 1276625 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting ASIC1a Reduces Innate Fear and Alters Neuronal Activity in the Fear Circuit
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Targeting ASIC1a Reduces Innate Fear and Alters Neuronal Activity in the Fear Circuit
چکیده انگلیسی

BackgroundThe molecular mechanisms underlying innate fear are poorly understood. Previous studies indicated that the acid sensing ion channel ASIC1a influences fear behavior in conditioning paradigms. However, these differences may have resulted from an ASIC1a effect on learning, memory, or the expression of fear.MethodsTo test the hypothesis that ASIC1a influences the expression of fear or anxiety independent of classical conditioning, we examined the effects of disrupting the mouse ASIC1a gene on unconditioned fear in the open field test, unconditioned acoustic startle, and fear evoked by the predator odor trimethylthiazoline (TMT). In addition, we tested the effects of acutely inhibiting ASIC1a with PcTx, an ASIC1a antagonist in tarantula venom. Our immunohistochemistry suggested ASIC1a is expressed in the bed nucleus of the stria terminalis, medial amygdala, and periaqueductal gray, which are thought to play important roles in the generation and expression of innate fear. Therefore, we also tested whether ASIC1a disruption altered c-fos expression in these structures following TMT exposure.ResultsWe found that the loss of ASIC1a reduced fear in the open field test, reduced acoustic startle, and inhibited the fear response to TMT. Similarly, intracerebroventricular administration of PcTx reduced TMT-evoked freezing in ASIC1a+/+ mice but not ASIC1a−/− mice. In addition, loss of ASIC1a altered TMT-evoked c-fos expression in the medial amydala and dorsal periaqueductal gray.ConclusionsThese findings suggest that ASIC1a modulates activity in the circuits underlying innate fear. Furthermore, the data indicate that targeting the ASIC1a gene or acutely inhibiting ASIC1a suppresses fear and anxiety independent of conditioning.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 62, Issue 10, 15 November 2007, Pages 1140–1148
نویسندگان
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