During retrieval, aversive memories become labile during a period known as the reconsolidation window. When an extinction procedure is performed within the reconsolidation window, the original aversive memory can be replaced by one that is less traumatic. Our recent studies revealed that acidosis via inhalation of carbon dioxide (CO2) during retrieval enhances memory lability. However, the effects of CO2 inhalation on the central nervous system can be extensive, and there is a lack of prior evidence suggesting that the effects of CO2 are selective to a reactivated memory. The specific effects of CO2 depend on acid-sensing ion channels (ASICs), proton receptors that are involved in synaptic transmission and plasticity in the amygdala. Our previous patch-clamping data suggests that CO2 inhalation during retrieval increases activities of neurons in the amygdala that involve in the memory trace. In addition, CO2 inhalation during retrieval increases exchanges from Ca2+-impermeable to Ca2+-permeable AMPA receptors. Thus, we hypothesize that CO2 selectively potentiates memory lability in mice when inhaled during retrieval of aversive memory. In addition, CO2 inhalation alters memory lability via synaptic plasticity at selectively targeted synapses. Alterations in spine morphology after CO2 and retrieval with a specific stimulus indicates that CO2 selectively enhances synaptic plasticity. Overall, our results suggest that inhaling CO2 during the retrieval event increases the lability of an aversive memory through a synapse-specific reconsolidation process.
bioRxiv Subject Collection: Neuroscience