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].

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.

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.

Homogeneity and long-term stability of tetracycline-regulated gene expression with low basal activity by using the rtTA2S-M2 transactivator and insulator-flanked reporter vectors

Gene ◽  
2004 ◽  
Vol 327 (1) ◽  
pp. 61-73 ◽  
Author(s):  
Zhican Qu ◽  
Jaideep V Thottassery ◽  
Sabrina Van Ginkel ◽  
Marina Manuvakhova ◽  
Louise Westbrook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Term Stability ◽  
Long Term Stability ◽  
Basal Activity ◽  
Regulated Gene Expression

Impairments to Consolidation, Reconsolidation, and Long-Term Memory Maintenance Lead to Memory Erasure

2020 ◽  
Vol 43 (1) ◽  
pp. 297-314 ◽  
Author(s):  
Josué Haubrich ◽  
Matteo Bernabo ◽  
Andrew G. Baker ◽  
Karim Nader
Keyword(s):  
Memory Trace ◽  
Direct Approach ◽  
Long Term Memory ◽  
Retrieval Failure ◽  
Term Memory ◽  
The Brain

An enduring problem in neuroscience is determining whether cases of amnesia result from eradication of the memory trace (storage impairment) or if the trace is present but inaccessible (retrieval impairment). The most direct approach to resolving this question is to quantify changes in the brain mechanisms of long-term memory (BM-LTM). This approach argues that if the amnesia is due to a retrieval failure, BM-LTM should remain at levels comparable to trained, unimpaired animals. Conversely, if memories are erased, BM-LTM should be reduced to resemble untrained levels. Here we review the use of BM-LTM in a number of studies that induced amnesia by targeting memory maintenance or reconsolidation. The literature strongly suggests that such amnesia is due to storage rather than retrieval impairments. We also describe the shortcomings of the purely behavioral protocol that purports to show recovery from amnesia as a method of understanding the nature of amnesia.

scholarly journals Control and Augmentation of Long-Term Plasmid Transgene ExpressionIn Vivoin Murine Muscle Tissue andEx Vivoin Patient Mesenchymal Tissue

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
David Morrissey ◽  
Jan P. van Pijkeren ◽  
Simon Rajendran ◽  
Sara A. Collins ◽  
Garrett Casey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgene Expression ◽  
Ex Vivo ◽  
Inducible Promoter ◽  
Luciferase Expression ◽  
Mesenchymal Tissue ◽  
Adenoviral Delivery ◽  
Regulated Gene Expression

Purpose. In vivogene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expressionin vivoin mice andex vivoin human tissues.Methods.Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadricepsin vivowas examined. Temporal control was assessed using a doxycycline-inducible system. Anex vivomodel was developed and optimised using murine tissue, and applied inex vivohuman tissue.Results. In vivoplasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detectedex vivoin human muscle and tendon.Conclusions.Plasmid constructs resulted in long-termin vivogene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in humanex vivomesenchymal tissue was demonstrated for the first time.

scholarly journals Novel Transcriptional Regulatory Signals in the Adeno-Associated Virus Terminal Repeat A/D Junction Element

2000 ◽  
Vol 74 (18) ◽  
pp. 8732-8739 ◽  
Author(s):  
Rebecca P. Haberman ◽  
Thomas J. McCown ◽  
Richard Jude Samulski
Keyword(s):  
Gene Expression ◽  
Fluorescent Protein ◽  
Terminal Repeat ◽  
Cmv Promoter ◽  
Adeno Associated Virus ◽  
Regulated Expression ◽  
Regulated Gene Expression

ABSTRACT Adeno-associated virus (AAV) type 2 vectors transfer stable, long-term gene expression to diverse cell types in vivo. Many gene therapy applications require the control of long-term transgene expression, and AAV vectors, similar to other gene transfer systems, are being evaluated for delivery of regulated gene expression cassettes. Previously, we (R. P. Haberman, T. J. McCown, and R. J. Samulski, Gene Ther. 5:1604–1611, 1998) demonstrated the use of the tetracycline-responsive system for long-term regulated expression in rat brains. In that study, we also observed residual expression in the “off” state both in vitro and in vivo, suggesting that the human cytomegalovirus (CMV) major immediate-early minimal promoter or other cis-acting elements (AAV terminal repeats [TR]) were contributing to this activity. In the present study, we identify that the AAV TR, minus the tetracycline-responsive minimal CMV promoter, will initiate mRNA expression from vector templates. Using deletion analysis and specific PCR-derived TR reporter gene templates, we mapped this activity to a 37-nucleotide stretch in theA/D elements of the TR. Although the mRNA derived from the TR is generated from a non-TATA box element, the use of mutant templates failed to identify function of canonical initiator sequences as previously described. Finally, we demonstrated the presence of green fluorescent protein expression both in vitro and in vivo in brain by using recombinant virus carrying only the TR element. Since the AAV terminal repeat is a necessary component of all recombinant AAV vectors, this TR transcriptional activity may interfere with all regulated expression cassettes and may be a problem in the development of novel TR split gene vectors currently being considered for genes too large to be packaged.

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