Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity

Collin J Kreple; Yuan Lu; Rebecca J Taugher; Andrea L Schwager-Gutman; Jianyang Du; Madeliene Stump; Yimo Wang; Ali Ghobbeh; Rong Fan; Caitlin V Cosme; Levi P Sowers; Michael J Welsh; Jason J Radley; Ryan T LaLumiere; John A Wemmie

doi:10.1038/nn.3750

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Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity

Journal article

Open access

Peer reviewed

Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity

Collin J Kreple, Yuan Lu, Rebecca J Taugher, Andrea L Schwager-Gutman, Jianyang Du, Madeliene Stump, Yimo Wang, Ali Ghobbeh, Rong Fan, Caitlin V Cosme, …

Nature neuroscience, Vol.17(8), pp.1083-1091

08/2014

DOI: 10.1038/nn.3750

PMCID: PMC4115047

PMID: 24952644

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https://www.ncbi.nlm.nih.gov/pmc/articles/4115047View

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Abstract

Acid-sensing ion channel 1A (ASIC1A) is abundant in the nucleus accumbens (NAc), a region known for its role in addiction. Because ASIC1A has been suggested to promote associative learning, we hypothesized that disrupting ASIC1A in the NAc would reduce drug-associated learning and memory. However, contrary to this hypothesis, we found that disrupting ASIC1A in the mouse NAc increased cocaine-conditioned place preference, suggesting an unexpected role for ASIC1A in addiction-related behavior. Moreover, overexpressing ASIC1A in rat NAc reduced cocaine self-administration. Investigating the underlying mechanisms, we identified a previously unknown postsynaptic current during neurotransmission that was mediated by ASIC1A and ASIC2 and thus well positioned to regulate synapse structure and function. Consistent with this possibility, disrupting ASIC1A altered dendritic spine density and glutamate receptor function, and increased cocaine-evoked plasticity, which resemble changes previously associated with cocaine-induced behavior. Together, these data suggest that ASIC1A inhibits the plasticity underlying addiction-related behavior and raise the possibility of developing therapies for drug addiction by targeting ASIC-dependent neurotransmission.

Synaptic Transmission - genetics

Neuronal Plasticity - drug effects

Male

Nucleus Accumbens - physiology

Excitatory Postsynaptic Potentials - drug effects

Behavior, Animal

Neuronal Plasticity - genetics

Cocaine-Related Disorders - metabolism

Female

Synaptic Transmission - drug effects

Cocaine - antagonists & inhibitors

Excitatory Postsynaptic Potentials - genetics

Disease Models, Animal

Nucleus Accumbens - pathology

Neural Inhibition - genetics

Mice, Inbred C57BL

Rats

Mice, Transgenic

Up-Regulation - genetics

Mice, Knockout

Acid Sensing Ion Channels - deficiency

Animals

Acid Sensing Ion Channels - physiology

Mice

Nucleus Accumbens - drug effects

Neural Inhibition - drug effects

Details

Title: Subtitle: Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity
Creators: Collin J Kreple - 1] Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, USA. Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, USA.
Yuan Lu - 1] Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA.
Rebecca J Taugher - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA
Andrea L Schwager-Gutman - Department of Psychology, University of Iowa, Iowa City, Iowa, USA
Jianyang Du - Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
Madeliene Stump - 1] Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, USA. Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA
Yimo Wang - Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA
Ali Ghobbeh - Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA
Rong Fan - Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA
Caitlin V Cosme - Department of Psychology, University of Iowa, Iowa City, Iowa, USA
Levi P Sowers - Department of Neurology, University of Iowa, Iowa City, Iowa, USA
Michael J Welsh - 1] Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, USA. Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA. Department of Psychology, University of Iowa, Iowa City, Iowa, USA. Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA. Howard Hughes Medical Institute, Iowa City, Iowa, USA
Jason J Radley - 1] Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA. Department of Psychology, University of Iowa, Iowa City, Iowa, USA
Ryan T LaLumiere - 1] Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA. Department of Psychology, University of Iowa, Iowa City, Iowa, USA
John A Wemmie - 1] Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, USA. Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA. Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA. Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA. Department of Veterans Affairs Medical Center, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.17(8), pp.1083-1091
DOI: 10.1038/nn.3750
PMID: 24952644
PMCID: PMC4115047
NLM abbreviation: Nat Neurosci
ISSN: 1546-1726
eISSN: 1546-1726
Publisher: United States
Grant note: R01 MH095972 / NIMH NIH HHS T32 NS045549 / NINDS NIH HHS DA034684 / NIDA NIH HHS Howard Hughes Medical Institute R01 DA034684 / NIDA NIH HHS T32 GM007337 / NIGMS NIH HHS T32NS045549 / NINDS NIH HHS 5R01MH085724 / NIMH NIH HHS I01 BX000741 / BLRD VA R01 MH085724 / NIMH NIH HHS R01 HL113863 / NHLBI NIH HHS MH095972 / NIMH NIH HHS R01HL113863 / NHLBI NIH HHS
Language: English
Date published: 08/2014
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neurology (Pediatrics); Neurosurgery; Internal Medicine
Record Identifier: 9984002346902771

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