Journal article
Targeting ASIC1a Reduces Innate Fear and Alters Neuronal Activity in the Fear Circuit
Biological psychiatry (1969), Vol.62(10), pp.1140-1148
2007
DOI: 10.1016/j.biopsych.2007.05.008
PMID: 17662962
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- Targeting ASIC1a Reduces Innate Fear and Alters Neuronal Activity in the Fear Circuit
- Creators
- Matthew W Coryell - Neuroscience Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaAdam E Ziemann - Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaPatricia J Westmoreland - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaJill M Haenfler - Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaZlatan Kurjakovic - Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaXiang-ming Zha - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaMargaret Price - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaMikael K Schnizler - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaJohn A Wemmie - Neuroscience Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Biological psychiatry (1969), Vol.62(10), pp.1140-1148
- DOI
- 10.1016/j.biopsych.2007.05.008
- PMID
- 17662962
- NLM abbreviation
- Biol Psychiatry
- ISSN
- 0006-3223
- eISSN
- 1873-2402
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000025, name: National Institute of Mental Health
- Language
- English
- Date published
- 2007
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984003408702771
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