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
Author Information
Erin E Koffman: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Charles M Kruse: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Kritika Singh: Department of Biological Sciences, University of Toledo, Toledo, Ohio, USA.
Farzaneh Sadat Naghavi: Department of Biological Sciences, University of Toledo, Toledo, Ohio, USA.
Melissa A Curtis: Department of Biological Sciences, University of Toledo, Toledo, Ohio, USA.
Jennifer Egbo: Department of Biological Sciences, University of Toledo, Toledo, Ohio, USA.
Mark Houdi: Department of Biological Sciences, University of Toledo, Toledo, Ohio, USA.
Boren Lin: Department of Biological Sciences, University of Toledo, Toledo, Ohio, USA.
Hui Lu: Department of Pharmacology and Physiology, George Washington University School of Medicine, Washington DC, USA.
Jacek Debiec: Molecular & Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.
Jianyang Du: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
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.
