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Title: Activation of acid‐sensing ion channels by carbon dioxide regulates amygdala synaptic protein degradation in memory reconsolidation
Authors: Lin, B
Alganem, K
O’Donovan, SM
Jin, Z
Naghavi, FS
Miller, OA
Ortyl, TC
Ruan, YC 
McCullumsmith, RE
Du, J
Issue Date: 2021
Source: Molecular brain, 2021, v. 14, 78
Abstract: Reconsolidation has been considered a process in which a consolidated memory is turned into a labile stage. Within the reconsolidation window, the labile memory can be either erased or strengthened. Manipulating acid-sensing ion channels (ASICs) in the amygdala via carbon dioxide (CO2) inhalation enhances memory retrieval and its lability within the reconsolidation window. Moreover, pairing CO2 inhalation with retrieval bears the reactivation of the memory trace and enhances the synaptic exchange of the calcium-impermeable AMPA receptors to calcium-permeable AMPA receptors. Our patch-clamp data suggest that the exchange of the AMPA receptors depends on the ubiquitin-proteasome system (UPS), via protein degradation. Ziram (50 µM), a ubiquitination inhibitor, reduces the turnover of the AMPA receptors. CO2 inhalation with retrieval boosts the ubiquitination without altering the proteasome activity. Several calcium-dependent kinases potentially involved in the CO2-inhalation regulated memory liability were identified using the Kinome assay. These results suggest that the UPS plays a key role in regulating the turnover of AMPA receptors during CO2 inhalation.
Keywords: Acid‐sensing ion channels
AMPA receptors
Aversive conditioning
Carbon dioxide
Memory retrieval
Protein degradation
Publisher: BioMed Central Ltd.
Journal: Molecular brain 
EISSN: 1756-6606
DOI: 10.1186/s13041-021-00786-7
Rights: © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.
The following publication Lin, B., Alganem, K., O’Donovan, S.M. et al. Activation of acid‐sensing ion channels by carbon dioxide regulates amygdala synaptic protein degradation in memory reconsolidation. Mol Brain 14, 78 (2021) is available at
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