Frequency selectivity, multistability, and oscillations emerge from models of genetic regulatory systems

1998 ◽  
Vol 274 (2) ◽  
pp. C531-C542 ◽  
Author(s):  
Paul Smolen ◽  
Douglas A. Baxter ◽  
John H. Byrne
Keyword(s):  
Cellular Response ◽  
Cultured Cells ◽  
Computational Approach ◽  
Long Term Memory ◽  
Mrna Levels ◽  
Complex Dynamic ◽  
Dynamic Activity ◽  
Regulatory Systems ◽  
Complex Models

To examine the capability of genetic regulatory systems for complex dynamic activity, we developed simple kinetic models that incorporate known features of these systems. These include autoregulation and stimulus-dependent phosphorylation of transcription factors (TFs), dimerization of TFs, crosstalk, and feedback. The simplest model manifested multiple stable steady states, and brief perturbations could switch the model between these states. Such transitions might explain, for example, how a brief pulse of hormone or neurotransmitter could elicit a long-lasting cellular response. In slightly more complex models, oscillatory regimes were identified. The addition of competition between activating and repressing TFs provided a plausible explanation for optimal stimulus frequencies that give maximal transcription. Such optimal frequencies are suggested by recent experiments comparing training paradigms for long-term memory formation and examining changes in mRNA levels in repetitively stimulated cultured cells. In general, the computational approach illustrated here, combined with appropriate experiments, provides a conceptual framework for investigating the function of genetic regulatory systems.

scholarly journals Temporally-precise basolateral amygdala activation is required for the formation of taste memories in gustatory cortex

2020 ◽  
Author(s):  
Elor Arieli ◽  
Ron Gerbi ◽  
Mark Shein-Idelson ◽  
Anan Moran
Keyword(s):  
Basolateral Amygdala ◽  
Time Lag ◽  
Nucleus Basalis ◽  
Electrophysiological Recording ◽  
Long Term Memory ◽  
Projection Neurons ◽  
Dynamic Activity ◽  
Gustatory Cortex ◽  
Taste Experience

AbstractLearning to associate malaise with the intake of novel food is critical for survival. Since food poisoning may take hours to affect, animals developed brain circuits to transform the current novel taste experience into a taste memory trace (TMT) and bridge this time lag. Ample studies showed that the basolateral amygdala (BLA), the nucleus basalis magnocellularis (NBM) and the gustatory cortex (GC) are involved in TMT formation and taste-malaise association. However, how dynamic activity across these brain regions during novel taste experience promotes the formation of these memories is currently unknown. We used the conditioned taste aversion (CTA) learning paradigm in combination with short-term optogenetics and electrophysiological recording in rats to test the hypothesis that temporally specific activation of BLA projection neurons is essential for TMT formation in the GC, and consequently CTA. We found that late-epoch (LE, >800ms), but not the early epoch (EE, 200-700ms), BLA activation during novel taste experience is essential for normal CTA, for early c-Fos expression in the GC (a marker of TMT formation) and for the subsequent changes in GC ensemble palatability coding. Interestingly, BLA activity was not required for intact taste identity or palatability perceptions. We further show that BLA-LE information is transmitted to GC through the BLA→NBM pathway where it affects the formation of taste memories. These results expose the dependence of long-term memory formation on specific temporal windows during sensory responses and the distributed circuits supporting this dependence.SignificanceConsumption of a novel taste may result in malaise and poses a threat to animals. Since the effects of poisoning appear only hours after consumption, animals must store the novel taste’s information in memory until they associate it with its value (nutritious or poisonous). Here we elucidate the neuronal activity patterns and circuits that support the processing and creation of novel-taste memories in rats. Our results show that specific patterns of temporal activation in the basolateral amygdala transmitted across brain areas are important for formation of taste memory and taste-malaise association. These findings may shed light on long-term activity-to-memory transformation in other sensory modalities.

scholarly journals The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Carmela Sidrauski ◽  
Anna M McGeachy ◽  
Nicholas T Ingolia ◽  
Peter Walter
Keyword(s):  
Mrna Translation ◽  
Ribosome Profiling ◽  
Stress Granule ◽  
Long Term Memory ◽  
Mrna Levels ◽  
Eif2α Phosphorylation ◽  
Genome Wide ◽  
Stressed Cells

Previously, we identified ISRIB as a potent inhibitor of the integrated stress response (ISR) and showed that ISRIB makes cells resistant to the effects of eIF2α phosphorylation and enhances long-term memory in rodents (<xref ref-type="bibr" rid="bib54">Sidrauski et al., 2013</xref>). Here, we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2α and induced no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2α phosphorylation, SG formation, and cognitive loss.

scholarly journals Genes Involved in Long-Term Memory Are Expressed in Testis of Cryptorchid Boys and Respond to GnRHa Treatment

2017 ◽  
Vol 152 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Faruk Hadziselimovic ◽  
Katharina Gegenschatz-Schmid ◽  
Gilvydas Verkauskas ◽  
Philippe Demougin ◽  
Vytautas Bilius ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Long Term Memory ◽  
Mrna Levels ◽  
Biological Processes ◽  
Term Memory ◽  
Rna Profiling ◽  
Intellectual Abilities ◽  
Neuronal Genes ◽  
Low Iq

It has been known for many years that boys with unilateral or bilateral undescended testis (cryptorchidism) tend to have a low IQ, and those who belong to the high infertility risk (HIR) group perform less well at school than low infertility risk (LIR) patients. However, the molecular biological processes underlying this phenomenon are not understood. In this study, we report the outcome of testicular RNA profiling for genes involved in long-term memory formation. We analyzed the histology and the transcriptome of testicular biopsies from bilateral HIR cryptorchid boys, comparing those who received GnRHa treatment for 6 months after the first surgery with those who did not receive GnRHa before the second surgery. We found that GnRHa treatment alters the testicular mRNA levels of neuronal genes that are involved in long-term memory and testosterone synthesis. These data highlight a possible molecular link between cryptorchidism, impaired mini-puberty, and diminished cognitive functions. Our results are consistent with the hypothesis that hypogonadotropic hypogonadism in cryptorchid boys with altered mini-puberty may affect neuronal genes important for memory and learning, which could help explaining the negative correlation between cryptorchidism and intellectual abilities.

scholarly journals Influence of theMelissa officinalisLeaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Marcin Ozarowski ◽  
Przemyslaw L. Mikolajczak ◽  
Anna Piasecka ◽  
Piotr Kachlicki ◽  
Radoslaw Kujawski ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Mrna Level ◽  
Significant Inhibition ◽  
Huperzine A ◽  
Long Term Memory ◽  
Cognitive Responses ◽  
Mrna Levels ◽  
Term Memory ◽  
Beta Secretase

Melissa officinalis(MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract ofMOleaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study,MOand HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, sinceMOproduced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus). However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms ofMOaction are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration.

scholarly journals lncRNA Neat1 drives neuronal histone methylation and age-related memory impairments

2019 ◽  
Author(s):  
Anderson A. Butler ◽  
Daniel R. Johnston ◽  
Simranjit Kaur ◽  
Farah D. Lubin
Keyword(s):  
Histone Methylation ◽  
Transcriptional Repression ◽  
Rna Binding ◽  
Gene Activation ◽  
Memory Formation ◽  
Long Term Memory ◽  
Mrna Levels ◽  
Term Memory ◽  
Age Related

AbstractHistone methylation is critical for the formation and maintenance of long-term memories. Long noncoding RNAs (lncRNAs) are regulators of histone methyltransferases and other chromatin modifying enzymes (CMEs). We investigated how lncRNA Neat1-mediated histone methylation contributes to hippocampus-dependent long-term memory formation, using a combination of transcriptomics, RNA binding protein immunoprecipitation, CRISPR mediated gene activation, and behavioral approaches. Suppression of the lncRNA Neat1 revealed widespread changes in gene transcription as well as perturbations of histone 3 lysine 9 dimethylation (H3K9me2), a repressive histone modification mark that is dysregulated in the aging hippocampus. We identified a Neat1-dependent mechanism of transcriptional repression via H3K9me2 at the c-Fos promoter corresponding with observed changes in c-Fos mRNA levels. Overexpression of hippocampal Neat1 via CRISPRa is sufficient to impair memory formation in young adults, recapitulating observed memory deficits in old adults, while Neat1 suppression in both young and old adult mice improves memory. These results suggest that lncRNA Neat1 is a potent epigenetic regulator of hippocampus-dependent long-term memory formation.

scholarly journals Long term memory of configural learning is enhanced via CREB upregulation by the flavonoid Quercetin in Lymnaea stagnalis

2021 ◽  
Author(s):  
Anuradha Batabyal ◽  
Veronica Rivi ◽  
Cristina Benatti ◽  
Johanna MC Blom ◽  
Ken Lukowiak
Keyword(s):  
Heat Stress ◽  
Lymnaea Stagnalis ◽  
Memory Formation ◽  
Long Term Memory ◽  
Pond Snail ◽  
Mrna Levels ◽  
Term Memory ◽  
Configural Learning ◽  
Flavonoid Quercetin

Animals respond to acute stressors by modifying their behaviour and physiology. The pond snail Lymnaea stagnalis exhibits configural learning (CL), a form of higher order associative learning. In CL snails develop a landscape of fear when they experience a predatory cue along with a taste of food. This experience results in a suppression of the food response; but the memory only persists for 3h. Lymnaea has been also found to upregulate heat shock proteins (HSPs) as a result of acute heat stress that leads to the enhancement of memory formation. A plant flavonoid quercetin blocks the upregulation of HSPs when experienced prior to heat stress. Here we used this blocking mechanism to test the hypothesis that HSP upregulation played a critical role in CL. Snails experienced quercetin prior to CL training and surprisingly instead of blocking memory formation it enhanced the memory such that it now persisted for at least 24h. Quercetin exposure both prior to or post CL enhanced long-term memory (LTM) up to 48h. We quantified CREB1 mRNA levels in the Lymnaea central nervous system following quercetin and found LymCREB1 to be upregulated following quercetin exposure. The enhanced LTM phenotype in L. stagnalis was most pronounced when quercetin was experienced during the consolidation phase. Additionally, quercetin exposure during the memory reconsolidation phase also led to memory enhancement. Thus, we found no support of our original hypothesis but found that quercetin exposure upregulated LymCREB1 leading to LTM formation for CL.

scholarly journals Improvement in Long-Term Memory following Chronic Administration ofEryngium planumRoot Extract in Scopolamine Model: Behavioral and Molecular Study

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Marcin Ozarowski ◽  
Barbara Thiem ◽  
Przemyslaw L. Mikolajczak ◽  
Anna Piasecka ◽  
Piotr Kachlicki ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Huperzine A ◽  
Control Group ◽  
Long Term Memory ◽  
Cognitive Responses ◽  
Mrna Levels ◽  
Term Memory ◽  
Saponin Content ◽  
Bace 1

Eryngium planumL. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots.

Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter
Keyword(s):  
Working Memory ◽  
Rapid Serial Visual Presentation ◽  
Language Comprehension ◽  
Short Term Memory ◽  
Visual Presentation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

Comparison of Auditory, Language, Memory, and Attention Abilities in Children With and Without Listening Difficulties

2020 ◽  
Vol 29 (4) ◽  
pp. 710-727
Author(s):  
Beula M. Magimairaj ◽  
Naveen K. Nagaraj ◽  
Alexander V. Sergeev ◽  
Natalie J. Benafield
Keyword(s):  
Auditory Processing ◽  
Short Term Memory ◽  
Group Differences ◽  
Long Term Memory ◽  
Short Term ◽  
Significant Group ◽  
Term Memory ◽  
Memory And Attention ◽  
Speed And Accuracy

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607

Retrieval from Memory or Procedural Strategies for Addition Problems

2011 ◽  
Vol 70 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Muriel Fanget ◽  
Catherine Thevenot ◽  
Caroline Castel ◽  
Michel Fayol
Keyword(s):  
Reaction Times ◽  
Long Term Memory ◽  
Verbal Reports ◽  
Term Memory ◽  
Simple Addition ◽  
Memory Traces ◽  
Addition Problem ◽  
Retrieval From Memory ◽  
Calculation Procedures

In this study, we used a paradigm recently developed ( Thevenot, Fanget, & Fayol, 2007 ) to determine whether 10-year-old children solve simple addition problems by retrieval of the answer from long-term memory or by calculation procedures. Our paradigm is unique in that it does not rely on reaction times or verbal reports, which are known to potentially bias the results, especially in children. Rather, it takes advantage of the fact that calculation procedures degrade the memory traces of the operands, so that it is more difficult to recognize them when they have been involved in the solution of an addition problem by calculation rather than by retrieval. The present study sharpens the current conclusions in the literature and shows that, when the sum of addition problems is up to 10, children mainly use retrieval, but when it is greater than 10, they mainly use calculation procedures.

Sign in / Sign up

Export Citation Format

Share Document