scholarly journals CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Xiao-Wen Yu ◽  
Daniel M Curlik ◽  
M Matthew Oh ◽  
Jerry CP Yin ◽  
John F Disterhoft
Keyword(s):  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Dorsal Hippocampus ◽  
Memory Deficits ◽  
Camp Response Element Binding ◽  
Intrinsic Excitability ◽  
Long Term Memory ◽  
Term Memory ◽  
Age Related

The molecular mechanisms underlying age-related cognitive deficits are not yet fully elucidated. In aged animals, a decrease in the intrinsic excitability of CA1 pyramidal neurons is believed to contribute to age-related cognitive impairments. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents facilitates cognition, and increases intrinsic excitability. However, it has yet to be tested if increasing CREB expression also ameliorates age-related behavioral and biophysical deficits. To test this hypothesis, we virally overexpressed CREB in CA1 of dorsal hippocampus. Rats received CREB or control virus, before undergoing water maze training. CREB overexpression in aged animals ameliorated the long-term memory deficits observed in control animals. Concurrently, cells overexpressing CREB in aged animals had reduced post-burst afterhyperpolarizations, indicative of increased intrinsic excitability. These results identify CREB modulation as a potential therapy to treat age-related cognitive decline.

Genes to remember

1999 ◽  
Vol 202 (21) ◽  
pp. 2887-2891
Author(s):  
C.M. Alberini
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Camp Response Element Binding ◽  
Long Term Memory ◽  
Biological Mechanisms ◽  
Camp Response Element ◽  
Term Memory ◽  
Molecular Approaches ◽  
Complex Forms

It has been known for several decades that the formation of long-term memory requires gene expression. In recent years, the use of genetic and molecular approaches has led to the identification and characterization of genes and molecules that play a fundamental role in the biological mechanisms underlying learning and memory. From these studies, it appears that molecules and molecular mechanisms essential for the process of memory have been conserved throughout evolution. The cyclic AMP (cAMP)-dependent activation pathway and a cAMP-dependent cascade of gene expression have been shown to be essential for memory formation in Aplysia californica, Drosophila melanogaster and rodents. Moreover, members of the transcription factor family cAMP response element binding proteins (CREBs) seem to represent key molecules for transforming incoming information into long-term memory. Here, we review the studies showing that conserved molecules and biological mechanisms are engaged in simple and complex forms of memory.

scholarly journals Deletion of Stk11 and Fos in mouse BLA projection neurons alters intrinsic excitability and impairs formation of long-term aversive memory

2019 ◽  
Author(s):  
David Levitan ◽  
Chenghao Liu ◽  
Tracy Yang ◽  
Yasuyuki Shima ◽  
Jian-You Lin ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Basolateral Amygdala ◽  
Molecular Mechanisms ◽  
Early Gene ◽  
Intrinsic Excitability ◽  
Long Term Memory ◽  
Projection Neurons ◽  
Term Memory ◽  
Growth Metabolism

AbstractConditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms are poorly understood, however. We used RNAseq from BLApn to identify learning-related changes in Stk11, a kinase with well-studied roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 restricted to BLApn completely blocks memory when occurring prior to training, but not following it, despite altering neither BLApn-dependent encoding of taste palatability in gustatory cortex, nor transcriptional activation of BLApn during training. Deletion of Stk11 in BLApn also increases their intrinsic excitability. Conversely, BLApn activated by CTA to express the immediate early gene Fos had reduced excitability. BLApn knockout of Fos also increased excitability and impaired learning. These data suggest that Stk11 and Fos expression play key roles in CTA long-term memory formation, perhaps by modulating the intrinsic excitability of BLApn.

Abstract P783: Alpha 7 -Acetylcholine Receptor Signaling Reduces Neuronal Apoptosis After Subarachnoid Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ari Dienel ◽  
Remya A Veettil ◽  
Kanako Matsumura ◽  
Peeyush Kumar T. ◽  
Spiros Blackburn ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Acetylcholine Receptor ◽  
Neuronal Apoptosis ◽  
Neuronal Survival ◽  
Memory Function ◽  
Memory Deficits ◽  
Long Term Memory ◽  
Term Memory ◽  
Receptor Knockout Mouse

Subarachnoid hemorrhage induces neuronal apoptosis which causes acute and long-term memory deficits. Ourhypothesis is that agonism of α7-acetylcholine receptors attenuates neuronal apoptosis and improves memorydeficits in SAH mice. Mice were randomly assigned into the experimental groups. One cohort was euthanizedone day after SAH to assess neuronal apoptosis and signaling pathways. A second cohort survived for 30 dayspost-SAH to test long-term memory function. Inhibitors and an α7-acetylcholine receptor knockout mouse wereused. Neurobehavioral performance was assessed on days 1-3, 5, 7, and 23-28. All outcomes were performedand all data was analyzed by a blinded investigator. The α7-acetylcholine receptor agonist prevented neuronalapoptosis and improved acute memory deficits caused by SAH via activation of the PI3K/Akt pathway in neurons.Agonism of the α7-acetylcholine receptor was beneficial in both male and female mice, although the protectionin females was significantly better than in male mice. α7-acetylcholine receptor agonism did not provide anybenefit in α7-acetylcholine receptor knockout mice subjected to SAH. Treatment with the α7-acetylcholinereceptor agonist for 3 days after SAH led to improved working memory one month after SAH suggesting thatacutely improving neuronal survival can have long-lasting benefits. The α7-acetylcholine receptor may be atherapeutic target for SAH which can promote neuronal survival acutely after SAH, but also confer long-lastingmemory benefits. The findings of this study support the α7-acetylcholine receptor as a treatment target whichmay attenuate the long-term memory deficits which SAH patients suffer from.

scholarly journals A Multivariate Assessment of Age-Related Cognitive Impairment in Octodon degus

2021 ◽  
Vol 15 ◽  
Author(s):  
Daniela S. Rivera ◽  
Carolina B. Lindsay ◽  
Carolina A. Oliva ◽  
Francisco Bozinovic ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Recognition Memory ◽  
Cognitive Performance ◽  
Natural Aging ◽  
Long Term Memory ◽  
Barnes Maze ◽  
Short Term ◽  
Term Memory ◽  
Age Related ◽  
Age Dependent

Aging is a progressive functional decline characterized by a gradual deterioration in physiological function and behavior. The most important age-related change in cognitive function is decline in cognitive performance (i.e., the processing or transformation of information to make decisions that includes speed of processing, working memory, and learning). The purpose of this study is to outline the changes in age-related cognitive performance (i.e., short-term recognition memory and long-term learning and memory) in long-lived Octodon degus. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects makes it a unique animal model for exploring the mechanisms underlying the behavioral and cognitive deficits related to natural aging. In this study, we examined young adult female degus (12- and 24-months-old) and aged female degus (38-, 56-, and 75-months-old) that were exposed to a battery of cognitive-behavioral tests. Multivariate analyses of data from the Social Interaction test or Novel Object/Local Recognition (to measure short-term recognition memory), and the Barnes maze test (to measure long-term learning and memory) revealed a consistent pattern. Young animals formed a separate group of aged degus for both short- and long-term memories. The association between the first component of the principal component analysis (PCA) from short-term memory with the first component of the PCA from long-term memory showed a significant negative correlation. This suggests age-dependent differences in both memories, with the aged degus having higher values of long-term memory ability but poor short-term recognition memory, whereas in the young degus an opposite pattern was found. Approximately 5% of the young and 80% of the aged degus showed an impaired short-term recognition memory; whereas for long-term memory about 32% of the young degus and 57% of the aged degus showed decreased performance on the Barnes maze test. Throughout this study, we outlined age-dependent cognitive performance decline during natural aging in degus. Moreover, we also demonstrated that the use of a multivariate approach let us explore and visualize complex behavioral variables, and identified specific behavioral patterns that allowed us to make powerful conclusions that will facilitate further the study on the biology of aging. In addition, this study could help predict the onset of the aging process based on behavioral performance.

scholarly journals Dissociating refreshing and elaboration and their impacts on memory

2018 ◽  
Author(s):  
Lea M. Bartsch ◽  
Vanessa M. Loaiza ◽  
Lutz Jäncke ◽  
Klaus Oberauer ◽  
Jarrod A. Lewis-Peacock
Keyword(s):  
Older Adults ◽  
Memory Performance ◽  
Ethics Committees ◽  
Fmri Data ◽  
Ethical Review ◽  
Long Term Memory ◽  
List Type ◽  
Term Memory ◽  
Age Related

AbstractMaintenance of information in working memory (WM) is assumed to rely on refreshing and elaboration, but clear mechanistic descriptions of these cognitive processes are lacking, and it is unclear whether they are simply two labels for the same process. This fMRI study investigated the extent to which refreshing, elaboration, and repeating of items in WM are distinct neural processes with dissociable behavioral outcomes in WM and long-term memory (LTM). Multivariate pattern analyses of fMRI data revealed differentiable neural signatures for these processes, which we also replicated in an independent sample of older adults. In some cases, the degree of neural separation within an individual predicted their memory performance. Elaboration improved LTM, but not WM, and this benefit increased as its neural signature became more distinct from repetition. Refreshing had no impact on LTM, but did improve WM, although the neural discrimination of this process was not predictive of the degree of improvement. These results demonstrate that refreshing and elaboration are separate processes that differently contribute to memory performance.HighlightsRepeated reading, refreshing, and elaboration are differentiable in brain activation patterns in both young and older adults.Elaboration selectively improved long-term memory for young adults, and the size of the benefit was related to the neural separability of elaboration from other processes.Older adults implemented a sub-optimal form of elaboration, and this may be a factor contributing to age-related deficits in long-term memory.Ethics statementThe study was approved by the ethical review board of the canton of Zurich (BASEC-No. 2017-00190) and all subjects gave informed written consent in accordance with the Declaration of Helsinki.Data and code availability statementAll behavioral data and analysis scripts can be assessed on the Open Science Framework (osf.io/p2h8b/). The fMRI data that support the findings of this study are available on request from the corresponding author, LMB. The fMRI data are not publicly available due to restrictions of the Swiss Ethics Committees on research involving humans regarding data containing information that could compromise the privacy of research participants.

Developmental exposure to methylmercury elicits early cell death in the cerebral cortex and long‐term memory deficits in the rat

2008 ◽  
Vol 27 (2) ◽  
pp. 165-174 ◽  
Author(s):  
Luca Ferraro ◽  
Maria Cristina Tomasini ◽  
Sergio Tanganelli ◽  
Roberta Mazza ◽  
Addolorata Coluccia ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Cortex ◽  
Memory Deficits ◽  
Long Term Memory ◽  
Developmental Exposure ◽  
Term Memory

scholarly journals SU30. Long-Term Memory Deficits in Schizophrenia: Are All Things Equal?

2017 ◽  
Vol 43 (suppl_1) ◽  
pp. S171-S172
Author(s):  
Susan Rossell
Keyword(s):  
Memory Deficits ◽  
Long Term Memory ◽  
Term Memory

PDE-7 Inhibitor BRL-50481 Reduces Neurodegeneration and Long-Term Memory Deficits in Mice Following Sevoflurane Exposure

2020 ◽  
Vol 11 (9) ◽  
pp. 1353-1358 ◽  
Author(s):  
Yingle Chen ◽  
Shunyuan Li ◽  
Xianmei Zhong ◽  
Zhenming Kang ◽  
Rulei Chen
Keyword(s):  
Memory Deficits ◽  
Long Term Memory ◽  
Term Memory

scholarly journals Selenofuranoside improves long-term memory deficits in rats after exposure to monosodium glutamate: Involvement of Na+, K+-ATPase activity

2018 ◽  
Vol 184 ◽  
pp. 27-33 ◽  
Author(s):  
Juliana Bernera Ramalho ◽  
Aryele Pinto Izaguirry ◽  
Melina Bucco Soares ◽  
Cristiano Chiapinotto Spiazzi ◽  
Natasha Frasson Pavin ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Monosodium Glutamate ◽  
Memory Deficits ◽  
Long Term Memory ◽  
Term Memory
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