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

Cited by 28 publications

(73 citation statements)

References 57 publications

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“…If CO2 reactivity is reflective of individual differences in susceptibility to respond to extinction treatment, it could also indicate a differential engagement of networks during extinction, which may make a candidate better suitable for an approach other than extinction (such as reconsolidation blockade or updating). Indeed, this idea would also be very much in line with a recent article showing that inhaling CO2 enhances the ability of retrieval to render an aversive memory labile (Du et al 2017). These findings appear in support of a reconsolidation-based hypothesis.…”

Section: Discussionsupporting

confidence: 62%

Predicting extinction phenotype to optimize fear reduction

Monfils

Lee

Keller³

et al. 2018

Psychopharmacology

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Fear conditioning is widely employed to study dysregulations of the fear system. The repeated presentation of a conditioned stimulus in the absence of a reinforcer leads to a decrease in fear responding-a phenomenon known as extinction. From a translational perspective, identifying whether an individual might respond well to extinction prior to intervention could prove important to treatment outcomes. Here, we test the hypothesis that CO reactivity predicts extinction phenotype in rats, and that variability in CO reactivity as well as extinction long-term memory (LTM) significantly predicts orexin activity in the lateral hypothalamus (LH). Our results validate a rat model of CO reactivity and show that subcomponents of behavioral reactivity following acute CO exposure explain a significant portion of the variance in extinction LTM. Furthermore, we show evidence that variability in CO reactivity is also significantly predictive of orexin activity in the LH, and that orexin activity, in turn, significantly accounts for LTM variance. Our findings open the possibility that we may be able to use CO reactivity as a screening tool to determine if individuals are good candidates for an extinction/exposure-based approach.

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Section: Discussionsupporting

confidence: 62%

Predicting extinction phenotype to optimize fear reduction

Monfils

Lee

Keller³

et al. 2018

Psychopharmacology

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“…5,7,[13][14][15] Effects of ASIC1A disruption on dendritic spine density and glutamate receptor composition and function have been reported, 7,13,15,16 as well as effects on long-term potentiation 5,7,17 and long-term depression. 5,7,[13][14][15] Effects of ASIC1A disruption on dendritic spine density and glutamate receptor composition and function have been reported, 7,13,15,16 as well as effects on long-term potentiation 5,7,17 and long-term depression.…”

mentioning

confidence: 99%

“…ASIC1A has been localized to dendritic spines, and implicated in synaptic plasticity and neurotransmission mediated by protons released from neurotransmitter containing vesicles. 5,7,[13][14][15] Effects of ASIC1A disruption on dendritic spine density and glutamate receptor composition and function have been reported, 7,13,15,16 as well as effects on long-term potentiation 5,7,17 and long-term depression. 12 Thus, through its location and function, ASIC1A may be well positioned to influence Pavlovian conditioning.…”

mentioning

confidence: 99%

A novel role for acid‐sensing ion channels in Pavlovian reward conditioning

Ghobbeh

Taugher

Alam

et al. 2018

Genes Brain and Behavior

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Pavlovian fear conditioning has been shown to depend on acid‐sensing ion channel‐1A (ASIC1A); however, it is unknown whether conditioning to rewarding stimuli also depends on ASIC1A. Here, we tested the hypothesis that ASIC1A contributes to Pavlovian conditioning to a non‐drug reward. We found effects of ASIC1A disruption depended on the relationship between the conditional stimulus (CS) and the unconditional stimulus (US), which was varied between five experiments. In experiment 1, when the CS preceded the US signaling an upcoming reward, Asic1a−/− mice exhibited a deficit in conditioning compared to Asic1a+/+ mice. Alternatively, in experiment 2, when the CS coinitiated with the US and signaled immediate reward availability, the Asic1a−/− mice exhibited an increase in conditioned responses compared to Asic1a+/+ mice, which contrasted with the deficits in the first experiment. Furthermore, in experiments 3 and 4, when the CS partially overlapped in time with the US, or the CS was shortened and coinitiated with the US, the Asic1a−/− mice did not differ from control mice. The contrasting outcomes were likely because of differences in conditioning because in experiment 5 neither the Asic1a−/− nor Asic1a+/+ mice acquired conditioned responses when the CS and US were explicitly unpaired. Taken together, these results suggest that the effects of ASIC1A disruption on reward conditioning depend on the temporal relationship between the CS and US. Furthermore, these results suggest that ASIC1A plays a critical, yet nuanced role in Pavlovian conditioning. More research will be needed to deconstruct the roles of ASIC1A in these fundamental forms of learning and memory.

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“…For example, studies of ASIC1a knockout mice showed that these animals exhibit reduced depression and anxiety related behavior [54], reduced fear behavior [55,56], and increased addiction related behavior [49]. Additionally, ASIC1a knockout mice display impaired performance in several learning paradigms, including hippocampal-dependent spatial learning and cerebellar-dependent eyeblink conditioning [57], amygdala-dependent impaired cue and contextual fear conditioning paradigms [51,[58][59][60][61], and impaired extinction of conditioned taste avoidance [53]. Similarly, mutations in the C. elegans ASIC-1 gene cause abnormal performance in an associative learning paradigm [62].…”

Section: Roles Of Deg/enacs In Behaviormentioning

confidence: 99%

The synaptic action of Degenerin/Epithelial sodium channels

Hill

Ben‐Shahar

2018

Channels

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Degenerin/Epithelial Sodium Channels (DEG/ENaCs) are a large family of animal-specific non-voltage gated ion channels, with enriched expression in neuronal and epithelial tissues. While neuronal DEG/ENaCs were originally characterized as sensory receptor channels, recent studies indicate that several DEG/ENaC family members are also expressed throughout the central nervous system. Human genome-wide association studies have linked DEG/ENaC-coding genes with several neurologic and psychiatric disorders, including epilepsy and panic disorder. In addition, studies in rodent models further indicate that DEG/ENaC activity in the brain contributes to many behaviors, including those related to anxiety and long-term memory. Although the exact neurophysiological functions of DEG/ENaCs remain mostly unknown, several key studies now suggest that multiple family members might exert their neuronal function via the direct modulation of synaptic processes. Here, we review and discuss recent findings on the synaptic functions of DEG/ENaCs in both vertebrate and invertebrate species, and propose models for their possible roles in synaptic physiology.

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

Cited by 28 publications

References 57 publications

Predicting extinction phenotype to optimize fear reduction

Predicting extinction phenotype to optimize fear reduction

A novel role for acid‐sensing ion channels in Pavlovian reward conditioning

The synaptic action of Degenerin/Epithelial sodium channels

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