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 7

CO2 inhalation during a selective memory retrieval enhances the retrieval-related memory trace.

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CO2 inhalation during a selective memory retrieval enhances the retrieva...
(A) Schematic showing the c-Fos-tTA-GFP mouse system combined with an AAV2-mCherry to label a specific memory trace. (B) An example image showing the efficiency of the expression of GFP and mCherry in the amygdala (scale bar: 500 μm). (C) The procedure of threat conditioning, memory retrieval, and memory trace labeling using the system in A. (D) Left, representative images of the neurons labeled by mCherry, GFP, and DAPI (scale bar: 200 μm); right, the enlarged area from the “merge” image showing the overlapping expression of mCherry and GFP neurons. The overlapping neurons indicate their “consanguinity” in the same memory trace (scale bar: 20 μm). (E) Summarized data are the percentage of the overlapping expression of mCherry and GFP neurons in different behavior groups. All mice underwent threat conditioning with a tone as the CS. One day later, the mice were separated into 4 groups for retrieval experiment. Data are mean ± SEM. n = 9 slices/3 mice for each group. *P < 0.05, by 1-way ANOVA with Tukey’s post hoc multiple-comparison test. (F) Control experiment showing the expression of mCherry with or without DOX as well as with or without threat conditioning. Data are mean ± SEM. n = 7 slices/3 mice for each group. ***P < 0.001 by unpaired 2-tailed Student’s t test.