scholarly journals Transcriptional Changes Before and After Forgetting of a Long-Term Sensitization Memory in Aplysia californica

2018 ◽  
Author(s):  
Robert Calin-Jageman ◽  
Irina Calin-Jageman
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Memory Trace ◽  
Aplysia Californica ◽  
Regulation Of Expression ◽  
Withdrawal Reflex ◽  
Before And After ◽  
Transcriptional Changes ◽  
Testable Model

This is a pre-print of a paper now published in Neurobiology of Learning and Memory: https://doi.org/10.1016/j.nlm.2018.09.007 Most long-term memories are forgotten, becoming progressively less likely to be recalled. Still, some memory fragments may persist beyond forgetting, as savings memory (easier relearning) can persist long after recall has become impossible. What happens to a memory trace during forgetting that makes it inaccessible for recall and yet still effective to spark easier re-learning? We are addressing this question by tracking the transcriptional changes that accompany learning and then forgetting of a long-term sensitization memory in the tail-elicited siphon withdrawal reflex of Aplysia californica. First, we tracked savings memory. We found that even though recall of sensitization fades completely within 1 week of training, savings memory is still robustly expressed at 2 weeks post training. Next, we tracked the time-course of regulation of 11 transcripts we previously identified as potentially being regulated beyond the decay of recall. Remarkably, 3 transcripts still show strong regulation of expression 2 weeks after training and an additional 4 are regulated for at least 1 week. These long-lasting changes in gene expression always began early in the memory process, within 1 day of training. We present a synthesis of our results tracking gene expression changes accompanying sensitization and provide a testable model of how sensitization memory is forgotten.

Stage 1 Registered Report Manuscript - Transcriptional Correlates of Savings Memory: Is Forgetting Due to Decay or Retrieval Failure?

2020 ◽  
Author(s):  
Robert Calin-Jageman ◽  
Irina Calin-Jageman ◽  
Tania Rosiles ◽  
Melissa Nguyen ◽  
Annette Garcia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Memory Trace ◽  
Aplysia Californica ◽  
Retrieval Failure ◽  
Initial Learning ◽  
Rigorous Test ◽  
Regulated Gene Expression ◽  
Stage 1 ◽  
Weak Similarity

[[This is a Stage 1 Registered Report manuscript. The project was submitted for review to eNeuro. Upon revision and acceptance, this version of the manuscript was pre-registered on the OSF (9/11/2019, https://osf.io/fqh8j) (but due to an oversight not posted as a preprint until July 2020). A Stage 2 manuscript is now posted as a pre-print (https://psyarxiv.com/h59jv) and is under review at eNeuro. A link to the final Stage 2 manuscript will be added when available.]]There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible due to retrieval failure. These different accounts of forgetting make different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is due to decay then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is due to retrieval-failure then savings should be mechanistically distinct from encoding. In this registered report we conducted a pre-registered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 day from training), a forgotten memory (8 days from training), and a savings memory (8 days from training but with a reminder on day 7 to evoke a long-term savings memory) for sensitization in Aplysia californica (n = 8 samples/group). We find that the transcriptional correlates of savings are [highly similar / somewhat similar / unique] relative to new (1-day-old) memories. Specifically, savings memory and a new memory share [X] of [Y] regulated transcripts, show [strong / moderate / weak] similarity in sets of regulated transcripts, and show [r] correlation in regulated gene expression, which is [substantially / somewhat / not at all] stronger than at forgetting. Overall, our results suggest that forgetting represents [decay / retrieval-failure / mixed mechanisms].

scholarly journals Transgenerational transcriptional heterogeneity from cytoplasmic chromatin

2022 ◽  
Author(s):  
Stamatis Papathanasiou ◽  
Nikos A. Mynhier ◽  
Shiwei Liu ◽  
Etai Jacob ◽  
Ema Stokasimov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Nuclear Architecture ◽  
Tumor Evolution ◽  
Histone 3 ◽  
Epigenetic State ◽  
Before And After ◽  
Transcriptional Changes ◽  
Cell Variation

Transcriptional heterogeneity from plasticity of the epigenetic state of chromatin is thought to contribute to tumor evolution, metastasis, and drug resistance. However, the mechanisms leading to nongenetic cell-to-cell variation in gene expression remain poorly understood. Here we demonstrate that heritable transcriptional changes can result from the formation of micronuclei, aberrations of the nucleus that are common in cancer. Micronuclei have fragile nuclear envelopes (NE) that are prone to spontaneous rupture, which exposes chromosomes to the cytoplasm and disrupts many nuclear activities. Using a combination of long-term live-cell imaging and same-cell, single-cell RNA sequencing (Look-Seq2), we identified significant reduction of gene expression in micronuclei, both before and after NE rupture. Furthermore, chromosomes in micronuclei fail to normally recover histone 3 lysine 27 acetylation, a critical step for the reestablishment of normal transcription after mitosis. These transcription and chromatin defects can persist into the next generation in a subset of cells, even after these chromosomes are incorporated into normal daughter nuclei. Moreover, persistent transcriptional repression is strongly associated with, and may be explained by, surprisingly long-lived DNA damage to these reincorporated chromosomes. Therefore, heritable alterations in transcription can originate from aberrations of nuclear architecture.

scholarly journals Transcriptional changes before and after forgetting of a long-term sensitization memory in Aplysia californica

2018 ◽  
Vol 155 ◽  
pp. 474-485
Author(s):  
Ushma Patel ◽  
Leticia Perez ◽  
Steven Farrell ◽  
Derek Steck ◽  
Athira Jacob ◽  
...  
Keyword(s):  
Aplysia Californica ◽  
Before And After ◽  
Transcriptional Changes

Registered Report: Transcriptional Analysis of Savings Memory Suggests Forgetting Is Due to Retrieval Failure

2020 ◽  
Author(s):  
Robert Calin-Jageman ◽  
Irina Calin-Jageman ◽  
Tania Rosiles ◽  
Melissa Nguyen ◽  
Annette Garcia ◽  
...  
Keyword(s):  
Memory Trace ◽  
Aplysia Californica ◽  
Transcriptional Response ◽  
Transcriptional Analysis ◽  
Retrieval Failure ◽  
Initial Learning ◽  
Rigorous Test ◽  
Stage 1 ◽  
Induced Changes

[[This is a Stage 2 Registered Report manuscript now accepted for publication at eNeuro. The accepted Stage 1 manuscript is posted here: https://psyarxiv.com/s7dft, and the pre-registration for the project is available here (https://osf.io/fqh8j, 9/11/2019). A link to the final Stage 2 manuscript will be posted after peer review and publication.]] There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible due to retrieval failure. These different accounts of forgetting lead to different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is due to decay, then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is due to retrieval failure, then savings should be mechanistically distinct from encoding. In this registered report we conducted a pre-registered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 day after training), a forgotten memory (8 days after training), and a savings memory (8 days after training but with a reminder on day 7 to evoke a long-term savings memory) for sensitization in Aplysia californica (n = 8 samples/group). We found that the re-activation of sensitization during savings does not involve a substantial transcriptional response. Thus, savings is transcriptionally distinct relative to a newer (1-day old) memory, with no co-regulated transcripts, negligible similarity in regulation-ranked ordering of transcripts, and a negligible correlation in training-induced changes in gene expression (r = .04 95% CI [-.12, .20]). Overall, our results suggest that forgetting of sensitization memory represents retrieval failure.

Cellular analysis of long-term habituation of the gill-withdrawal reflex of Aplysia californica

Science ◽  
1978 ◽  
Vol 202 (4374) ◽  
pp. 1306-1308 ◽  
Author(s):  
V. Castellucci ◽  
T. Carew ◽  
E. Kandel
Keyword(s):  
Aplysia Californica ◽  
Withdrawal Reflex ◽  
Cellular Analysis

scholarly journals Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice

2006 ◽  
Vol 27 (3) ◽  
pp. 187-200 ◽  
Author(s):  
Colin Selman ◽  
Nicola D. Kerrison ◽  
Anisha Cooray ◽  
Matthew D. W. Piper ◽  
Steven J. Lingard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Caloric Restriction ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Cellular Transport ◽  
Expression Of Genes ◽  
Transcriptional Changes

Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies. Multitissue transcriptional changes and concomitant metabolic responses to acute CR have not been described. We generated whole genome RNA transcript profiles in liver, skeletal muscle, colon, and hypothalamus and simultaneously measured plasma metabolites using proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle showed increased gene expressions associated with fatty acid metabolism and a reduction in those involved in hepatic lipid biosynthesis. Glucogenic amino acids increased in plasma, and gene expression for hepatic gluconeogenesis was enhanced. Increased expression of genes for hormone-mediated signaling and decreased expression of genes involved in protein binding and development occurred in hypothalamus. Cell proliferation genes were decreased and cellular transport genes increased in colon. Acute CR captured many, but not all, hepatic transcriptional changes of long-term CR. Our findings demonstrate a clear transcriptional response across multiple tissues during acute CR, with congruent plasma metabolite changes. Liver and muscle switched gene expression away from energetically expensive biosynthetic processes toward energy conservation and utilization processes, including fatty acid metabolism and gluconeogenesis. Both muscle and colon switched gene expression away from cellular proliferation. Mice undergoing acute CR rapidly adopt many transcriptional and metabolic changes of long-term CR, suggesting that the beneficial effects of CR may require only a short-term reduction in caloric intake.

scholarly journals Nickel-induced transcriptional changes persist  post exposure through epigenetic reprogramming

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Cynthia C. Jose ◽  
Zhenjia Wang ◽  
Vinay Singh Tanwar ◽  
Xiaoru Zhang ◽  
Chongzhi Zang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modification ◽  
Lung Epithelial Cells ◽  
Differentially Expressed ◽  
Nickel Ions ◽  
Post Exposure ◽  
Genome Wide ◽  
Transcriptional Changes ◽  
Nickel Exposure

Abstract Background Nickel is an occupational and environmental toxicant associated with a number of diseases in humans including pulmonary fibrosis, bronchitis and lung and nasal cancers. Our earlier studies showed that the nickel-exposure-induced genome-wide transcriptional changes, which persist even after the termination of exposure may underlie nickel pathogenesis. However, the mechanisms that drive nickel-induced persistent changes to the transcriptome remain elusive. Results To elucidate the mechanisms that underlie nickel-induced long-term transcriptional changes, in this study, we examined the transcriptome and the epigenome of human lung epithelial cells during nickel exposure and after the termination of exposure. We identified two categories of persistently differentially expressed genes: (i) the genes that were differentially expressed during nickel exposure; and (ii) the genes that were differentially expressed only after the termination of exposure. Interestingly, > 85% of the nickel-induced gene expression changes occurred only after the termination of exposure. We also found extensive genome-wide alterations to the activating histone modification, H3K4me3, after the termination of nickel exposure, which coincided with the post-exposure gene expression changes. In addition, we found significant post-exposure alterations to the repressive histone modification, H3K27me3. Conclusion Our results suggest that while modest first wave of transcriptional changes occurred during nickel exposure, extensive transcriptional changes occurred during a second wave of transcription for which removal of nickel ions was essential. By uncovering a new category of transcriptional and epigenetic changes, which occur only after the termination of exposure, this study provides a novel understanding of the long-term deleterious consequences of nickel exposure on human health.

Long-term facilitation alters transmitter releasing properties at the crayfish neuromuscular junction

1986 ◽  
Vol 55 (3) ◽  
pp. 484-498 ◽  
Author(s):  
J. M. Wojtowicz ◽  
H. L. Atwood
Keyword(s):  
Neuromuscular Junction ◽  
Synaptic Transmission ◽  
Time Course ◽  
Muscle Fibers ◽  
Low Frequencies ◽  
Before And After ◽  
Binomial Parameter ◽  
Small Muscle ◽  
Long Term Facilitation

Synaptic transmission at the neuromuscular junction of the excitatory axon supplying the crayfish opener muscle was examined before and after induction of long-term facilitation (LTF) by a 10-min period of stimulation at 20 Hz. Induction of LTF led to a period of enhanced synaptic transmission, which often persisted for many hours. The enhancement was entirely presynaptic in origin, since quantal unit size and time course were not altered, and quantal content of transmission (m) was increased. LTF was not associated with any persistent changes in action potential or presynaptic membrane potential recorded in the terminal region of the excitatory axon. The small muscle fibers of the walking-leg opener muscle were almost isopotential, and all quantal events could be recorded with an intracellular microelectrode. In addition, at low frequencies of stimulation, m was small. Thus it was possible to apply a binomial model of transmitter release to events recorded from individual muscle fibers and to calculate values for n (number of responding units involved in transmission) and p (probability of transmission for the population of responding units) before and after LTF. In the majority of preparations analyzed (6/10), amplitude histograms of evoked synaptic potentials could be described by a binomial distribution with a small n and moderately high p. LTF produced a significant increase in n, while p was slightly reduced. The results can be explained by a model in which the binomial parameter n represents the number of active synapses and parameter p the mean probability of release at a synapse. Provided that a pool of initially inactive synapses exists, one can postulate that LTF involves recruitment of synapses to the active state.

scholarly journals Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 107-122 ◽  
Author(s):  
Sky K Feuer ◽  
Xiaowei Liu ◽  
Annemarie Donjacour ◽  
Rhodel Simbulan ◽  
Emin Maltepe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Preimplantation Embryo ◽  
Environmental Exposures ◽  
Developmental Time ◽  
Transcriptional Responses ◽  
Transcriptional Changes ◽  
Specific Impact

Stressful environmental exposures incurred early in development can affect postnatal metabolic health and susceptibility to non-communicable diseases in adulthood, although the molecular mechanisms by which this occurs have yet to be elucidated. Here, we use a mouse model to investigate how assortedin vitroexposures restricted exclusively to the preimplantation period affect transcription both acutely in embryos and long term in subsequent offspring adult tissues, to determine if reliable transcriptional markers ofin vitrostress are present at specific developmental time points and throughout development. Eachin vitrofertilization or embryo culture environment led to a specific and unique blastocyst transcriptional profile, but we identified a common 18-gene and 9-pathway signature of preimplantation embryo manipulation that was present in allin vitroembryos irrespective of culture condition or method of fertilization. This fingerprint did not persist throughout development, and there was no clear transcriptional cohesion between adult IVF offspring tissues or compared to their preceding embryos, indicating a tissue-specific impact ofin vitrostress on gene expression. However, the transcriptional changes present in each IVF tissue were targeted by the same upstream transcriptional regulators, which provide insight as to how acute transcriptional responses to stressful environmental exposures might be preserved throughout development to influence adult gene expression.

scholarly journals Reference genes for gene expression analysis in the fungal pathogen Neonectria ditissima and their use demonstrating expression up-regulation of candidate virulence genes

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0238157
Author(s):  
Liz M. Florez ◽  
Reiny W. A. Scheper ◽  
Brent M. Fisher ◽  
Paul W. Sutherland ◽  
Matthew D. Templeton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Reference Genes ◽  
Time Course ◽  
Gene Expression Analysis ◽  
Virulence Genes ◽  
Functional Characterization ◽  
Post Inoculation ◽  
In Planta ◽  
Regulation Of Expression

European canker, caused by the necrotrophic fungal phytopathogen Neonectria ditissima, is one of the most damaging apple diseases worldwide. An understanding of the molecular basis of N. ditissima virulence is currently lacking. Identification of genes with an up-regulation of expression during infection, which are therefore probably involved in virulence, is a first step towards this understanding. Reverse transcription quantitative real-time PCR (RT-qPCR) can be used to identify these candidate virulence genes, but relies on the use of reference genes for relative gene expression data normalisation. However, no report that addresses selecting appropriate fungal reference genes for use in the N. ditissima-apple pathosystem has been published to date. In this study, eight N. ditissima genes were selected as candidate RT-qPCR reference genes for gene expression analysis. A subset of the primers (six) designed to amplify regions from these genes were specific for N. ditissima, failing to amplify PCR products with template from other fungal pathogens present in the apple orchard. The efficiency of amplification of these six primer sets was satisfactory, ranging from 81.8 to 107.53%. Analysis of expression stability when a highly pathogenic N. ditissima isolate was cultured under 10 regimes, using the statistical algorithms geNorm, NormFinder and BestKeeper, indicated that actin and myo-inositol-1-phosphate synthase (mips), or their combination, could be utilised as the most suitable reference genes for normalisation of N. ditissima gene expression. As a test case, these reference genes were used to study expression of three candidate virulence genes during a time course of infection. All three, which shared traits with fungal effector genes, had up-regulated expression in planta compared to in vitro with expression peaking between five and six weeks post inoculation (wpi). Thus, these three genes may well be involved in N. ditissima pathogenicity and are priority candidates for further functional characterization.

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