The Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala During the First Extinction Episode Has Persistent Effects on Extinction Expression

Lay, Belinda P. P.; Koya, Eisuke; Hope, Bruce T.; Esber, Guillem R.; Iordanova, Mihaela D.

doi:10.1016/j.biopsych.2022.07.021

Cited by 8 publications

(8 citation statements)

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“…It has been suggested that extinction does not permanently eliminate fear memory, suggesting that a new engram is established that competes with the original one to drive the behavior (Lacagnina et al, 2019; Lay et al, 2022). To assess this, we infused Daun02 into the BLA of animals subjected to extinction training (Supplementary 2A in Data S1) and no difference was found between the groups during Test 1, before the drug infusion (Student's t ‐test, T 6 = 0.1898, p = .8557) or during Test 2, after the drug infusion (Student's t ‐test, T 6 = 0.5306, p = .6148) (Supplementary 2B and Supplementary file 5 in Data S1 for detailed statistics).…”

Section: Resultsmentioning

confidence: 99%

“…The reduction in fear response during extinction is thought to be regulated by central nucleus of the amygdala (CeA) activity and its bidirectional connectivity with the mPFC and BLA (Bocchio et al, 2017; Lee & Kaang, 2023). While Zhang et al (2020) found that extinction memory engram is formed and stored within a specific neuronal population of the BLA, Lay et al (2022) showed that extinction training recruits the CeA (but not BLA) extinction engram to prevent fear expression. Although the divergences found in these studies might be explained by protocol differences, our results could not eliminate the extinction engram in the BLA, regardless of the weak or strong extinction protocol presented.…”

Section: Discussionmentioning

confidence: 99%

“…The Daun02 method uses c‐Fos‐lacZ transgenic rats, in which β‐galactosidase (β‐gal) and Fos are co‐expressed within strongly activated neurons (Cruz et al, 2013; Cruz et al, 2014; Cruz et al, 2015; Koya et al, 2016; Lay et al, 2022). The c‐Fos‐lacZ transgene in transgenic rats contains a c‐Fos promoter that controls the transcription of the lacZ coding sequence.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, in strongly activated neurons β‐gal converts Daun02 into Daunorubicin, which disrupts the normal function of these neurons, inducing the apoptosis of those neurons (Cruz et al, 2013). The experimental design was based on prior studies using similar objectives (Cruz et al, 2013; Cruz et al, 2014; Cruz et al, 2015; Koya et al, 2016; Lay et al, 2022).…”

Section: Methodsmentioning

confidence: 99%

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Distinct engrams control fear and extinction memory

Luft,

Popik,

Gonçalves

et al. 2024

Hippocampus

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Memories are stored in engram cells, which are necessary and sufficient for memory recall. Recalling a memory might undergo reconsolidation or extinction. It has been suggested that the original memory engram is reactivated during reconsolidation so that memory can be updated. Conversely, during extinction training, a new memory is formed that suppresses the original engram. Nonetheless, it is unknown whether extinction creates a new engram or modifies the original fear engram. In this study, we utilized the Daun02 procedure, which uses c‐Fos‐lacZ rats to induce apoptosis of strongly activated neurons and examine whether a new memory trace emerges as a result of a short or long reactivation, or if these processes rely on modifications within the original engram located in the basolateral amygdala (BLA) and infralimbic (IL) cortex. By eliminating neurons activated during consolidation and reactivation, we observed significant impacts on fear memory, highlighting the importance of the BLA engram in these processes. Although we were unable to show any impact when removing the neurons activated after the test of a previously extinguished memory in the BLA, disrupting the IL extinction engram reactivated the aversive memory that was suppressed by the extinction memory. Thus, we demonstrated that the IL cortex plays a crucial role in the network involved in extinction, and disrupting this specific node alone is sufficient to impair extinction behavior. Additionally, our findings indicate that extinction memories rely on the formation of a new memory, supporting the theory that extinction memories rely on the formation of a new memory, whereas the reconsolidation process reactivates the same original memory trace.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Distinct engrams control fear and extinction memory

Luft,

Popik,

Gonçalves

et al. 2024

Hippocampus

View full text Add to dashboard Cite

show abstract

“…Lay et al ( 2023 ) microinjected Daun02 in Fos-lacZ transgenic rats following a single extinction training episode. They reported that the initial extinction-recruited central nucleus of the amygdala (CN) ensemble was critical to the acquisition-extinction balance and that greater behavioral restoration did not imply weaker extinction contribution.…”

Section: Chemical-based Activity-dependent Tools Based On Immediate E...mentioning

confidence: 99%

Exploring the memory: existing activity-dependent tools to tag and manipulate engram cells

Pang,

Wu,

Chen

et al. 2024

Front. Cell. Neurosci.

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The theory of engrams, proposed several years ago, is highly crucial to understanding the progress of memory. Although it significantly contributes to identifying new treatments for cognitive disorders, it is limited by a lack of technology. Several scientists have attempted to validate this theory but failed. With the increasing availability of activity-dependent tools, several researchers have found traces of engram cells. Activity-dependent tools are based on the mechanisms underlying neuronal activity and use a combination of emerging molecular biological and genetic technology. Scientists have used these tools to tag and manipulate engram neurons and identified numerous internal connections between engram neurons and memory. In this review, we provide the background, principles, and selected examples of applications of existing activity-dependent tools. Using a combination of traditional definitions and concepts of engram cells, we discuss the applications and limitations of these tools and propose certain developmental directions to further explore the functions of engram cells.

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