Author response: Transient acidosis while retrieving a fear-related memory enhances its lability

Du, Jianyang; Price, Margaret P.; Taugher, Rebecca J.; Grigsby, Daniel; Ash, Jamison J; Stark, Austin C; Saad, Zubayer Hossain; Singh, Kritika; Mandal, Juthika; Wemmie, John A.; Welsh, Michael J.

doi:10.7554/elife.22564.018

Cited by 3 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because inhaling 10% CO 2 during the labile period induced by cued fear retrieval further enhanced memory lability (Du et al, 2017), we hypothesized that exposing mice to 10% CO 2 1 h after acquisition, during the time period in which new memories are thought to be labile (Mednick et al, 2011), would also alter fear memory. Thus, we trained mice in a cued fear conditioning paradigm in which we paired an auditory cue with a foot shock and 1 h later mice were placed in a different context and exposed mice to air or 10% CO 2 .…”

Section: Resultsmentioning

confidence: 99%

“…Conversion of short term fear memory to long lasting memory (i.e., consolidation) has been previously found to require both CP-AMPAR insertion (Rumpel et al, 2005;Nedelescu et al, 2010), and CREB phosphorylation and subsequent changes in gene transcription (Alberini, 2009). Previously, it was shown that when coupled with memory reactivation, CO 2 exposure also increased both insertion of CP-AMPARs and CREB phosphorylation, which may be critical for promoting susceptibility of the fear memory to subsequent modification (Du et al, 2017). The potential role of ASIC1A in CREB phosphorylation has not been tested.…”

Section: Discussionmentioning

confidence: 99%

“…ASIC1A is abundantly expressed in the amygdala (Wemmie et al, 2003;Coryell et al, 2007;Price et al, 2014;Chiang et al, 2015), and manipulating ASIC1A in the amygdala alters cued and context fear memory (Coryell et al, 2008;Chiang et al, 2015), as well as CO 2 -evoked freezing (Ziemann et al, 2009). Likewise, localized acidosis in the amygdala promotes freezing (Ziemann et al, 2009) and plasticity (Du et al, 2017). However, ASIC1A is also expressed in several other fear circuit structures in which it could influence fear memory, such as the bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, prefrontal, and cingulate cortices (Wemmie et al, 2003;Coryell et al, 2007;Price et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study found that if mice inhaled 10% carbon dioxide (CO 2 ) during retrieval, cued fear memory was made more labile than with retrieval alone, making it more susceptible to modification via subsequent extinction or reconditioning. CO 2 inhalation during cued retrieval facilitated insertion of Ca2 +permeable AMPA receptors (CP-AMPARs), increased cAMPresponse element binding protein (CREB) phosphorylation and re-activated a greater percentage of neurons in the memory trace as compared to retrieval alone (Du et al, 2017). In addition to being labile after a retrieval event, fear memories are labile for a period of time immediately following acquisition during which they are vulnerable to disruption (Schafe and LeDoux, 2000;Duvarci et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, Du et al found that the CO 2 effect on cued retrieval depended on the acid-sensing ion channel-1 (ASIC1A; Du et al, 2017). ASIC1A is a synaptic cation channel that is activated when extracellular pH drops (Waldmann et al, 1997;Wemmie et al, 2002Wemmie et al, , 2013Zha et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Table_1.pdf

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Table_1.pdf

View full text Add to dashboard Cite

Proton receptors regulate synapse-specific reconsolidation in the amygdala

Koffman

Kruse

Singh

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Post-acquisition CO2 Inhalation Enhances Fear Memory and Depends on ASIC1A

Taugher

Wunsch

Wang

et al. 2021

Front. Behav. Neurosci.

View full text Add to dashboard Cite

A growing body of evidence suggests that memories of fearful events may be altered after initial acquisition or learning. Although much of this work has been done in rodents using Pavlovian fear conditioning, it may have important implications for fear memories in humans such as in post-traumatic stress disorder (PTSD). A recent study suggested that cued fear memories, made labile by memory retrieval, were made additionally labile and thus more vulnerable to subsequent modification when mice inhaled 10% carbon dioxide (CO2) during retrieval. In light of this finding, we hypothesized that 10% CO2 inhalation soon after fear acquisition might affect memory recall 24 h later. We found that both cue and context fear memory were increased by CO2 exposure after fear acquisition. The effect of CO2 was time-dependent, as CO2 inhalation administered 1 or 4 h after cued fear acquisition increased fear memory, whereas CO2 inhalation 4 h before or 24 h after cued fear acquisition did not increase fear memory. The ability of CO2 exposure following acquisition to enhance fear memory was not a general consequence of stress, as restraining mice after acquisition did not alter cued fear memory. The memory-enhancing action of CO2 may be relatively specific to fear conditioning as novel object recognition was impaired by post-training CO2 inhalation. To explore the molecular underpinnings of these effects, we tested if they depended on the acid-sensing ion channel-1a (ASIC1A), a proton-gated cation channel that mediates other effects of CO2, likely via its ability to sense acidosis induced during CO2 inhalation. We found that CO2 inhalation did not alter cued or context fear memory in Asic1a–/– mice, suggesting that this phenomenon critically depends on ASIC1A. These results suggest that brain acidosis around the time of a traumatic event may enhance memory of the trauma, and may thus constitute an important risk factor for developing PTSD. Moreover, preventing peritraumatic acidosis might reduce risk of PTSD.

show abstract

Author response: Transient acidosis while retrieving a fear-related memory enhances its lability

Cited by 3 publications

References 0 publications

Table_1.pdf

Table_1.pdf

Proton receptors regulate synapse-specific reconsolidation in the amygdala

Post-acquisition CO2 Inhalation Enhances Fear Memory and Depends on ASIC1A

Contact Info

Product

Resources

About