The bed nucleus of the stria terminalis is critical for anxiety-related behavior evoked by CO2 and acidosis

Rebecca J Taugher; Yuan Lu; Yimo Wang; Collin J Kreple; Ali Ghobbeh; Rong Fan; Levi P Sowers; John A Wemmie

doi:10.1523/JNEUROSCI.1680-14.2014

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The bed nucleus of the stria terminalis is critical for anxiety-related behavior evoked by CO2 and acidosis

Journal article

Open access

Peer reviewed

The bed nucleus of the stria terminalis is critical for anxiety-related behavior evoked by CO2 and acidosis

Rebecca J Taugher, Yuan Lu, Yimo Wang, Collin J Kreple, Ali Ghobbeh, Rong Fan, Levi P Sowers and John A Wemmie

The Journal of neuroscience, Vol.34(31), pp.10247-10255

07/30/2014

DOI: 10.1523/JNEUROSCI.1680-14.2014

PMCID: PMC4115136

PMID: 25080586

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Abstract

Carbon dioxide (CO2) inhalation lowers brain pH and induces anxiety, fear, and panic responses in humans. In mice, CO2 produces freezing and avoidance behavior that has been suggested to depend on the amygdala. However, a recent study in humans with bilateral amygdala lesions revealed that CO2 can trigger fear and panic even in the absence of amygdalae, suggesting the importance of extra-amygdalar brain structures. Because the bed nucleus of the stria terminalis (BNST) contributes to fear- and anxiety-related behaviors and expresses acid-sensing ion channel-1A (ASIC1A), we hypothesized that the BNST plays an important role in CO2-evoked fear-related behaviors in mice. We found that BNST lesions decreased both CO2-evoked freezing and CO2-conditioned place avoidance. In addition, we found that CO2 inhalation caused BNST acidosis and that acidosis was sufficient to depolarize BNST neurons and induce freezing behavior; both responses depended on ASIC1A. Finally, disrupting Asic1a specifically in the BNST reduced CO2-evoked freezing, whereas virus-vector-mediated expression of ASIC1A in the BNST of Asic1a(-/-) and Asic1a(+/+) mice increased CO2-evoked freezing. Together, these findings identify the BNST as an extra-amygdalar fear circuit structure important in CO2-evoked fear-related behavior.

Motor Activity - physiology

Septal Nuclei - injuries

Septal Nuclei - physiology

Motor Activity - drug effects

Phosphopyruvate Hydratase - metabolism

Green Fluorescent Proteins - genetics

Septal Nuclei - cytology

Glial Fibrillary Acidic Protein - metabolism

Freezing Reaction, Cataleptic - drug effects

Acidosis - complications

Neurons - physiology

Neurons - drug effects

Disease Models, Animal

Green Fluorescent Proteins - metabolism

Mice, Inbred C57BL

Mice, Transgenic

Acid Sensing Ion Channels - deficiency

Patch-Clamp Techniques

Animals

Carbon Dioxide - toxicity

Electrolysis

Acid Sensing Ion Channels - genetics

Avoidance Learning - drug effects

Mice

In Vitro Techniques

Anxiety - etiology

Plethysmography

Details

Title: Subtitle: The bed nucleus of the stria terminalis is critical for anxiety-related behavior evoked by CO2 and acidosis
Creators: Rebecca J Taugher - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa 52242, Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242
Yuan Lu - Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242
Yimo Wang - Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242
Collin J Kreple - Medical Scientist Training Program, University of Iowa, Iowa City, Iowa 52242, Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242
Ali Ghobbeh - Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242
Rong Fan - Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242
Levi P Sowers - Department of Neurology, University of Iowa, Iowa City, Iowa 52242
John A Wemmie - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa 52242, Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, Medical Scientist Training Program, University of Iowa, Iowa City, Iowa 52242, Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, Department of Neurosurgery, University of Iowa, Iowa City, Iowa 52242, and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52246 john-wemmie@uiowa.edu
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.34(31), pp.10247-10255
DOI: 10.1523/JNEUROSCI.1680-14.2014
PMID: 25080586
PMCID: PMC4115136
NLM abbreviation: J Neurosci
ISSN: 0270-6474
eISSN: 1529-2401
Publisher: United States
Grant note: T32 NS045549 / NINDS NIH HHS R01 MH085724 / NIMH NIH HHS R01 HL113863 / NHLBI NIH HHS T32 GM007337 / NIGMS NIH HHS T32NS045549 / NINDS NIH HHS 5R01MH085724 / NIMH NIH HHS I01 BX000741 / BLRD VA R01HL113863 / NHLBI NIH HHS
Language: English
Date published: 07/30/2014
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurology (Pediatrics); Neurosurgery
Record Identifier: 9984003420702771

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