Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior

John A Wemmie; Matthew W Coryell; Candice C Askwith; Ejvis Lamani; A. Soren Leonard; Curt D Sigmund; Michael J Welsh

doi:10.1073/pnas.0308753101

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Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior

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Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior

John A Wemmie, Matthew W Coryell, Candice C Askwith, Ejvis Lamani, A. Soren Leonard, Curt D Sigmund and Michael J Welsh

Proceedings of the National Academy of Sciences - PNAS, Vol.101(10), pp.3621-3626

03/09/2004

DOI: 10.1073/pnas.0308753101

PMCID: PMC373512

PMID: 14988500

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Abstract

The acid-sensing ion channel 1a (ASIC1a) is abundantly expressed in the amygdala complex and other brain regions associated with fear. Studies of mice with a disrupted ASIC1 gene suggested that ASIC1a may contribute to learned fear. To test this hypothesis, we generated mice overexpressing human ASIC1a by using the pan-neuronal synapsin 1 promoter. Transgenic ASIC1a interacted with endogenous mouse ASIC1a and was distributed to the synaptosomal fraction of brain. Transgenic expression of ASIC1a also doubled neuronal acid-evoked cation currents. The amygdala showed prominent expression, and overexpressing ASIC1a enhanced fear conditioning, an animal model of acquired anxiety. These data raise the possibility that ASIC1a and H + -gated currents may contribute to the development of abnormal fear and to anxiety disorders in humans.

Biological Sciences

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Title: Subtitle: Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior
Creators: John A Wemmie - Veterans Affairs Medical Center, Iowa City, IA 52242
Matthew W Coryell - Veterans Affairs Medical Center, Iowa City, IA 52242
Candice C Askwith - Veterans Affairs Medical Center, Iowa City, IA 52242
Ejvis Lamani - Veterans Affairs Medical Center, Iowa City, IA 52242
A. Soren Leonard - Veterans Affairs Medical Center, Iowa City, IA 52242
Curt D Sigmund - Veterans Affairs Medical Center, Iowa City, IA 52242
Michael J Welsh - Veterans Affairs Medical Center, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.101(10), pp.3621-3626
DOI: 10.1073/pnas.0308753101
PMID: 14988500
PMCID: PMC373512
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 03/09/2004
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Neurosurgery; Internal Medicine
Record Identifier: 9984003997302771

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