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
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
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Research Article Neuroscience

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

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 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.

Authors

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

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Figure 1

CO2 inhalation during a selective memory retrieval potentiates the effect of the extinction.

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CO2 inhalation during a selective memory retrieval potentiates the effec...
(A) Schematic protocol for threat conditioning (Threat Cond.), memory retrieval, extinction (Ext), memory test–spontaneous recovery (Spon Rec), and renewal. On day 1, the mice were subjected to 3 pure tones and 3 white noises paired with 6 foot-shocks in context A. One day after, the mice were placed in context B and were subjected to both tone and noise as retrieval events. Thirty minutes after retrieval, the mice were treated with 2 blocks of extinctions with a pure tone as the CS. On day 7, Spon Rec and renewal were tested individually in context B and then context A. During each memory testing, 4 pure tones and 4 white noises were presented as CSs. (B–E) Data are presented by the percentage of freezing time during the CSs (tone and noise) in threat conditioning (B), retrievals (tone and noise) (C), 2 sections of extinction with tone (D), memory test of Spon Rec and renewal with tone and noise (E). (F–I) Data are presented by the percentage of freezing time during the CSs (tone and noise) in threat conditioning (F), retrievals (tone plus CO2 inhalation and noise) (G), 2 sections of extinction with tone (H), Spon Rec, and renewal with tone and noise (I). (J and K) Comparison data based on Spon Rec and renewal, respectively, from E and I. Data are mean ± SEM. n = 12 mice in each group. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, by 2-tailed paired Student’s t test (E and I) or 1-way ANOVA with Tukey’s post hoc multiple-comparison test (J and K).