Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning

John A Wemmie; Candice C Askwith; Ejvis Lamani; Martin D Cassell; John H. Freeman Jr; Michael J Welsh

doi:10.1523/jneurosci.23-13-05496.2003

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Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning

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Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning

John A Wemmie, Candice C Askwith, Ejvis Lamani, Martin D Cassell, John H. Freeman Jr and Michael J Welsh

The Journal of neuroscience, Vol.23(13), pp.5496-5502

07/02/2003

DOI: 10.1523/jneurosci.23-13-05496.2003

PMCID: PMC6741257

PMID: 12843249

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Abstract

The acid-sensing ion channel, ASIC1, contributes to synaptic plasticity in the hippocampus and to hippocampus-dependent spatial memory. To explore the role of ASIC1 in brain, we examined the distribution of ASIC1 protein. Surprisingly, although ASIC1 was present in the hippocampal circuit, it was much more abundant in several areas outside the hippocampus. ASIC1 was enriched in areas with strong excitatory synaptic input such as the glomerulus of the olfactory bulb, whisker barrel cortex, cingulate cortex, striatum, nucleus accumbens, amygdala, and cerebellar cortex. Because ASIC1 levels were particularly high in the amygdala, we focused further on this area. We found that extracellular acidosis elicited a greater current density in amygdala neurons than hippocampal neurons and that disrupting the ASIC1 gene eliminated H+-evoked currents in the amygdala. We also tested the effect of ASIC1 on amygdala-dependent behavior; ASIC1-null mice displayed deficits in cue and context fear conditioning, yet baseline fear on the elevated plus maze was intact. These studies suggest that ASIC1 is distributed to regions supporting high levels of synaptic plasticity and contributes to the neural mechanisms of fear conditioning.

Fear - physiology

RNA, Messenger - metabolism

Brain - physiology

Brain - metabolism

Synapses - metabolism

Sodium Channels - metabolism

Neurons - metabolism

Sodium Channels - deficiency

Brain - cytology

Maze Learning - physiology

Acid Sensing Ion Channels

Acoustic Stimulation

Amygdala - metabolism

Cells, Cultured

Amygdala - cytology

Behavior, Animal - physiology

Nerve Tissue Proteins

Hippocampus - cytology

Conditioning, Classical - physiology

Mice, Knockout

Membrane Proteins

Hippocampus - metabolism

Patch-Clamp Techniques

Animals

Mice

Sodium Channels - genetics

Details

Title: Subtitle: Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning
Creators: John A Wemmie - Department of Psychiatry, Neuroscience Graduate Program, Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA. john-wemmie@uiowa.edu
Candice C Askwith
Ejvis Lamani
Martin D Cassell
John H. Freeman Jr
Michael J Welsh
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.23(13), pp.5496-5502
DOI: 10.1523/jneurosci.23-13-05496.2003
PMID: 12843249
PMCID: PMC6741257
NLM abbreviation: J Neurosci
ISSN: 1529-2401
eISSN: 1529-2401
Publisher: United States
Grant note: NS-38890 / NINDS NIH HHS DK-25295 / NIDDK NIH HHS
Language: English
Date published: 07/02/2003
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Anatomy and Cell Biology; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
Record Identifier: 9984004097002771

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