Acid-sensing ion channel 1a regulates the specificity of reconsolidation of conditioned threat responses

Erin E. Koffman; Charles M. Kruse; Kritika Singh; Farzaneh Sadat Naghavi; Melissa A. Curtis; Jennifer Egbo; Mark Houdi; Boren Lin; Hui Lu; Jacek Debiec; Jianyang Du

doi:10.1172/jci.insight.155341

Acid-sensing ion channel 1a regulates the specificity of reconsolidation of conditioned threat responses

Erin E. Koffman,¹ Charles M. Kruse,¹ Kritika Singh,¹ Farzaneh Sadat Naghavi,¹ Melissa A. Curtis,¹ Jennifer Egbo,¹ Mark Houdi,¹ Boren Lin,¹ Hui Lu,² Jacek Debiec,³ and Jianyang Du⁴

Published January 13, 2022 - More info

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Abstract

Recent research on altering threat memory has focused on a reconsolidation window. During reconsolidation, threat memories are retrieved and become labile. Reconsolidation of distinct threat memories is synapse-dependent whereas the underlying regulatory mechanism of the specificity of reconsolidation is poorly understood. We designed a unique behavioral paradigm in which a distinct threat memory can be retrieved through the associated conditioned stimulus. In addition, we proposed a regulatory mechanism by which the activation of acid-sensing ion channels (ASICs), strengthens the distinct memory trace associated with the memory reconsolidation to determine its specificity. The activation of ASICs by carbon dioxide (CO₂) inhalation when paired with memory retrieval, triggers the reactivation of the distinct memory trace, resulting in greater memory lability. ASICs potentiate the memory trace by altering the amygdala-dependent synaptic transmission and plasticity at selectively targeted synapses. Our results suggest that inhaling CO₂ during the retrieval event increases the lability of a threat memory through a synapse-specific reconsolidation process.

Acid-sensing ion channel 1a regulates the specificity of reconsolidation of conditioned threat responses

Erin E. Koffman,¹ Charles M. Kruse,¹ Kritika Singh,¹ Farzaneh Sadat Naghavi,¹ Melissa A. Curtis,¹ Jennifer Egbo,¹ Mark Houdi,¹ Boren Lin,¹ Hui Lu,² Jacek Debiec,³ and Jianyang Du⁴

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Acid-sensing ion channel 1a regulates the specificity of reconsolidation of conditioned threat responses

Erin E. Koffman,1 Charles M. Kruse,1 Kritika Singh,1 Farzaneh Sadat Naghavi,1 Melissa A. Curtis,1 Jennifer Egbo,1 Mark Houdi,1 Boren Lin,1 Hui Lu,2 Jacek Debiec,3 and Jianyang Du4

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Erin E. Koffman,¹ Charles M. Kruse,¹ Kritika Singh,¹ Farzaneh Sadat Naghavi,¹ Melissa A. Curtis,¹ Jennifer Egbo,¹ Mark Houdi,¹ Boren Lin,¹ Hui Lu,² Jacek Debiec,³ and Jianyang Du⁴