Background
The 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.
Methods
To 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.
Results
We 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.
Conclusions
These 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.
Key Words
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Article info
Publication history
Published online: July 28, 2007
Accepted:
May 10,
2007
Received in revised form:
April 27,
2007
Received:
March 14,
2007
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
