Small G protein RAC‐2 regulates forgetting via the JNK‐1 signalling pathway in <scp><i>Caenorhabditis elegans</i></scp>

Bai, Hua; Huang, Hui; Zhao, Ninghui; Gu, Huan; Li, Yixin; Zou, Wei; Wu, Tingting; Huang, Xiaowei

doi:10.1111/ejn.15855

Cited by 5 publications

(6 citation statements)

References 43 publications

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“…Our results suggest that blocking arachidonic acid release with 4-BPB can slow the forgetting of sensitization in Aplysia , though we cannot rule out effect sizes that would be too small to regularly detect with achievable sample sizes. This finding provides qualified support for the idea that forgetting of sensitization is an active process and documents another phylum in the animal kingdom (Mollusca) in which forgetting can be manipulated through alterations in second-messenger signaling ( Liu et al, 2016 ; Zhang et al, 2018 ; Bai et al, 2022 ; O’Leary et al, 2023 ). Definitive evidence for active forgetting of sensitization will require replication and examining if enhancing arachidonic acid release can speed forgetting.…”

Section: Discussionsupporting

confidence: 68%

“…For example, in fruit flies forgetting of an olfactory memory is produced through postlearning activation of a set of dopaminergic neurons; blocking this activity forestalls forgetting and enhancing activation speeds forgetting ( Berry et al, 2012 ; Himmelreich et al, 2017 ). In addition, the Rho family of G proteins seem to play an evolutionarily conserved role in forgetting, as manipulation of Rac1 bidirectionally regulates forgetting in mice ( Liu et al, 2016 ; O’Leary et al, 2023 ) and flies ( Shuai et al, 2010 ; Zhang et al, 2018 ) and Rac2 plays a similar role in Caenorhabditis elegans ( Bai et al, 2022 ). Active forgetting mechanisms can be coupled to behavior and thus can contribute not only to spontaneous/passive forgetting but also to interference-based forms of forgetting ( Berry et al, 2018 ; Zhang et al, 2018 ) and to modulation of forgetting by sleep ( Berry et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Evidence of Active-Forgetting Mechanisms? Blocking Arachidonic Acid Release May Slow Forgetting of Sensitization inAplysia

Calin-Jageman,

Gonzalez Delgadillo,

Gamino

et al. 2024

eNeuro

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Long-term sensitization inAplysiais accompanied by a persistent up-regulation of mRNA encoding the peptide neurotransmitter Phe-Met-Arg-Phe-amide (FMRFa), a neuromodulator that opposes the expression of sensitization through activation of the arachidonic-acid second-messenger pathway. We completed a pre-registered test of the hypothesis that FMRFa plays a critical role in the forgetting of sensitization.Aplysiareceived long-term sensitization training and were then given whole-body injections of vehicle (N= 27), FMRFa (N= 26), or 4-bromophenacylbromide (4-BPB;N= 31), a phospholipase inhibitor that prevents the release of arachidonic acid. FMRFa produced no changes in forgetting. 4-BPB decreased forgetting measured 6 days after training (ds= 0.55 95% CI[0.01, 1.09]), though the estimated effect size is uncertain. Our results provide preliminary evidence that forgetting of sensitization may be a regulated, active process inAplysia, but could also indicate a role for arachidonic acid in stabilizing the induction of sensitization.Significance StatementForgetting plays an essential role in memory function as both excessive and insufficient forgetting are related to profound disruptions of mental health. Our results provide preliminary evidence that the forgetting of sensitization inAplysiais a regulated process that can be delayed by blocking arachidonic acid production. This work contributes to ongoing efforts to understand the neurobiology of forgetting.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Evidence of Active-Forgetting Mechanisms? Blocking Arachidonic Acid Release May Slow Forgetting of Sensitization inAplysia

Calin-Jageman,

Gonzalez Delgadillo,

Gamino

et al. 2024

eNeuro

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“…Our finding that inhibition of the proteasome does not extend memory duration is consistent with both a mechanism in which protein synthesis is necessary for formation of the memory engram but does not itself constitute it, or with a proteasome-independent mechanism of engram decay (for example, free cellular proteases). Genes mediating active processes of forgetting in C. elegans have been identified (Arai et al, 2022;Bai et al, 2022;Hadziselimovic et al, 2014;Inoue et al, 2013;Teo et al, 2022) 1). The C. elegans memory we describe here does not clearly correspond to any of these: it depends on transcription and translation, is independent of CREB, and is produced through a single massed training session.…”

Section: The Identity Of Gene Products Requiring Translation Remains ...mentioning

confidence: 99%

A NovelC. elegansMemory Type Mediated by an Insulin/Phospholipase C Pathway

Merritt

Udachina

Freidel

et al. 2023

Preprint

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Memories are often categorized into types, reflecting their behavioural, anatomical and molecular diversity: these classifications both aid understanding of the differences among varieties of memory and help delineate the unifying cross-species principles underlying them. In the nematode wormCaenorhabditis elegans, we find that an associative memory of the pairing of the normally attractive odorant benzaldehyde and starvation depends on de novo transcription and translation, is independent of CREB, and is produced by massed training: a pattern which does not correspond to any of the well-characterized molecular categories of invertebrate memory. Further, as has been shown for many memories in vertebrates, but not previously in nematodes, we find that formation of this memory continues after removal of the stimuli initially causing it, and that it is labile to disruption through protein synthesis inhibition following training, but that inhibition of proteasomal activity does not extend the duration of the memory. Previous findings have implicated insulin pathway signalling as a key component of this benzaldehyde/starvation memory, however we find that the transcriptional activity required for the memory is likely to be independent of the transcription factors that function at the terminus of this pathway. These findings better characterize this model associative memory in relation to other invertebrate memory types and identify ways in which it both shares their traits and differs from them.

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“…Interestingly, although Rho family small G proteins (e.g. Rac1, Cdc42) are required for forgetting through modulating the actin cytoskeleton [ 96 , 97 ], the C. elegans Rho family member RAC-2 also regulates forgetting, but independently of actin dynamics [ 98 ].…”

Section: The Role Of Dopamine In Learning Memory and Forgettingmentioning

confidence: 99%

Neural mechanisms of dopamine function in learning and memory in Caenorhabditis elegans

McMillen,

Chew

2023

Neuronal Signaling

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Research into learning and memory over the past decades has revealed key neurotransmitters that regulate these processes, many of which are evolutionarily conserved across diverse species. The monoamine neurotransmitter dopamine is one example of this, with countless studies demonstrating its importance in regulating behavioural plasticity. However, dopaminergic neural networks in the mammalian brain consist of hundreds or thousands of neurons, and thus cannot be studied at the level of single neurons acting within defined neural circuits. The nematode Caenorhabditis elegans has an experimentally tractable nervous system with a completely characterised synaptic connectome. This makes it an advantageous system to undertake mechanistic studies into how dopamine encodes lasting yet flexible behavioural plasticity in the nervous system. In this Review, we synthesise the research to date exploring the importance of dopaminergic signalling in learning, memory formation, and forgetting, focusing on research in C. elegans. We also explore the potential for dopamine-specific fluorescent biosensors in C. elegans to visualise dopaminergic neural circuits during learning and memory formation, in real-time. We propose that the use of these sensors in C. elegans, in combination with optogenetic and other light-based approaches, will further illuminate the detailed spatiotemporal requirements for encoding behavioural plasticity in an accessible experimental system. Understanding the key molecules and circuit mechanisms that regulate learning and forgetting in more compact invertebrate nervous systems may reveal new druggable targets for enhancing memory storage and delaying memory loss in bigger brains.

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Small G protein RAC‐2 regulates forgetting via the JNK‐1 signalling pathway in Caenorhabditis elegans

Cited by 5 publications

References 43 publications

Evidence of Active-Forgetting Mechanisms? Blocking Arachidonic Acid Release May Slow Forgetting of Sensitization inAplysia

Evidence of Active-Forgetting Mechanisms? Blocking Arachidonic Acid Release May Slow Forgetting of Sensitization inAplysia

A NovelC. elegansMemory Type Mediated by an Insulin/Phospholipase C Pathway

Neural mechanisms of dopamine function in learning and memory in Caenorhabditis elegans

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