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The Regulation of Gene Expression During Memory Consolidation in the Hippocampus

The Regulation of Gene Expression During Memory Consolidation in the Hippocampus PDF Author: Shane Gary Poplawski
Publisher:
ISBN:
Category :
Languages : en
Pages : 438

Book Description
Memory consolidation is the process through which short-term memories are stabilized for long-term retention. New gene expression is required for this process to occur successfully. Although gene expression is a necessary component for memory consolidation, the targets and regulation of this gene expression are not well understood. The advent of next-generation sequencing technologies has provided a tremendous resource to probe important questions genome-wide in ways that were previously impossible. In this dissertation, I use next-generation sequencing to investigate the transcriptional targets of learning in the hippocampus. Chapter 1 reviews the previous research on the regulation of gene expression during memory consolidation. Previous work has implicated histone acetylation as an epigenomic modification that regulates long-term memory. In Chapter 2, I use RNA-seq to investigate the gene expression changes that occur 30 minutes after contextual fear conditioning. I use recently developed analysis techniques to improve our ability to detect changes and study alternative splicing genome-wide for the first time after learning. Chapter 3 investigates whether these gene expression changes are specific to contextual fear conditioning or shared with other hippocampus-dependent learning tasks such as object-location memory. I find that the transcriptional targets are similar between training paradigms, but their temporal activation differs. In Chapter 4, we use ChIP-seq, Sono-seq and MNase-seq to determine changes in histone acetylation, chromatin accessibility and nucleosome positioning that occur in response to learning. I find only small changes in H3K9/14ac, but large changes in chromatin accessibility. This may suggest that a multitude of histone modifications act in concert to regulate chromatin accessibility during memory consolidation.

The Regulation of Gene Expression During Memory Consolidation in the Hippocampus

The Regulation of Gene Expression During Memory Consolidation in the Hippocampus PDF Author: Shane Gary Poplawski
Publisher:
ISBN:
Category :
Languages : en
Pages : 438

Book Description
Memory consolidation is the process through which short-term memories are stabilized for long-term retention. New gene expression is required for this process to occur successfully. Although gene expression is a necessary component for memory consolidation, the targets and regulation of this gene expression are not well understood. The advent of next-generation sequencing technologies has provided a tremendous resource to probe important questions genome-wide in ways that were previously impossible. In this dissertation, I use next-generation sequencing to investigate the transcriptional targets of learning in the hippocampus. Chapter 1 reviews the previous research on the regulation of gene expression during memory consolidation. Previous work has implicated histone acetylation as an epigenomic modification that regulates long-term memory. In Chapter 2, I use RNA-seq to investigate the gene expression changes that occur 30 minutes after contextual fear conditioning. I use recently developed analysis techniques to improve our ability to detect changes and study alternative splicing genome-wide for the first time after learning. Chapter 3 investigates whether these gene expression changes are specific to contextual fear conditioning or shared with other hippocampus-dependent learning tasks such as object-location memory. I find that the transcriptional targets are similar between training paradigms, but their temporal activation differs. In Chapter 4, we use ChIP-seq, Sono-seq and MNase-seq to determine changes in histone acetylation, chromatin accessibility and nucleosome positioning that occur in response to learning. I find only small changes in H3K9/14ac, but large changes in chromatin accessibility. This may suggest that a multitude of histone modifications act in concert to regulate chromatin accessibility during memory consolidation.

The Transcriptional Regulation of Memory

The Transcriptional Regulation of Memory PDF Author: Benedict C. Albensi
Publisher: Frontiers Media SA
ISBN: 2889198650
Category : Neurosciences. Biological psychiatry. Neuropsychiatry
Languages : en
Pages : 118

Book Description
The formation of various forms of memory involves a series of distinct cellular and molecular mechanisms, many of which are not fully understood. There are highly conserved pathways that are involved in learning, memory, and synaptic plasticity, which is the primary substrate for memory storage. The formation of short-term (across minutes) memory is mediated by local changes in synapses, while long-term (across hours to days) memory storage is associated with activation of transcription and synthesis of proteins that modify synaptic function. Transcription factors, which can either repress or activate transcription, play a vital role in driving protein synthesis underlying synaptic plasticity and memory, whereby protein synthesis provides the necessary building blocks to accommodate structural changes at the synapse that foster memory formation. Recent data implicate several families of transcription factors that appear critically important in the regulation of memory. In this Topic we will focus on the families of transcription factors thus far found to be critically involved in synaptic plasticity and memory formation. These include cAMP response element binding protein (CREB), Rel/nuclear factor B (Rel/NFB), CCAAT enhancer binding protein (C/EBP), and early growth response factor (Egr). In recent years, numerous studies have implicated epigenetic mechanisms, changes in gene activity and expression that occur without alteration in gene sequence, in the memory consolidation process. DNA methylation and chromatin remodeling are critically involved in learning and memory, supporting a role of epigenetic mechanisms. Here we provide more evidence of the importance of DNA methylation, histone posttranslational modifications and the role of histone acetylation and HDAC inhibitors in above mentioned processes.

The Role of the Chromatin Modifying Enzymes CBP and HDAC3 in Long-term Memory Processes

The Role of the Chromatin Modifying Enzymes CBP and HDAC3 in Long-term Memory Processes PDF Author: Ruth Michelle Barrett
Publisher:
ISBN: 9781124880877
Category :
Languages : en
Pages : 105

Book Description
It has long been appreciated that the expression of specific genes is required for long-term memory storage, but the molecular mechanisms responsible for the regulation of transcription during memory consolidation remain the subject of intense investigation. Recently, several studies have demonstrated a pivotal role for the histone acetylation in memory and synaptic plasticity. Therefore, this dissertation focuses on the role of chromatin modifying enzymes, specifically CBP and HDAC3, in regulating gene expression in the hippocampus, a brain region involved in spatial and contextual memory, during long-term memory formation. I show here, using genetic and pharmacological methods, that CBP and HDAC3 have critical roles in the hippocampus in acetylating specific histone residues, regulating activity-dependent gene expression, and long-term memory formation. Further, I demonstrate that the effect of a loss of CBP cannot be compensated for by the inhibition of HDACs and that immediate early gene Nr4a2 is necessary for the enhancement of memory by HDAC3 inhibition. Together my results indicate a role for the balance of histone acetylation and deacetylation during long-term memory formation, specifically carried out by CBP and HDAC3.

Novel Mechanisms of Memory

Novel Mechanisms of Memory PDF Author: Karl Peter Giese
Publisher: Springer
ISBN: 3319243640
Category : Medical
Languages : en
Pages : 190

Book Description
This book integrates discoveries from recent years to show the diversity of molecular mechanisms that contribute to memory consolidation, reconsolidation, extinction, and forgetting. It provides a special focus on the processes that govern functional and structural plasticity of dendritic spines. In nine chapters, new and important ideas related to learning and memory processes will be presented. Themes discussed include the role of AMPA receptors in memory, two signalling cascades involved in local spine remodelling and memory, the role of extracellular matrix proteins in memory, the regulation of gene expression and protein translation, and mechanisms of retrieval-induced memory modulation and forgetting. We believe that the study of these topics represents a great step toward understanding the complexity of the brain and the processes it governs.

Molecular Basis of Memory

Molecular Basis of Memory PDF Author:
Publisher: Academic Press
ISBN: 0124202004
Category : Science
Languages : en
Pages : 467

Book Description
This special volume of Progress in Molecular Biology and Translational Science provides a current overview of how memory is processed in the brain. A broad range of topics are presented by leaders in the field, ranging from brain circuitry to synaptic plasticity to the molecular machinery that contributes to the brain's ability to maintain information across time. Memory systems in the prefrontal cortex, hippocampus and amygdala are considered as well. In addition, the volume covers recent contributions to our understanding of memory from in vivo imaging, optogenetic, electrophysiological, biochemical and molecular biological studies. Articles from world renowned experts in memory Covering topics from signaling, epigenetic, RNA translation to plasticity Methodological approaches include molecular and cellular, behavioral, electrophysiological, optogenetic and functional imaging

CREB-mediated Enhancement of Hippocampus-dependent Memory Consolidation and Reconsolidation

CREB-mediated Enhancement of Hippocampus-dependent Memory Consolidation and Reconsolidation PDF Author: Melanie Jay Sekeres
Publisher:
ISBN:
Category :
Languages : en
Pages :

Book Description


Neural Plasticity and Memory

Neural Plasticity and Memory PDF Author: Federico Bermudez-Rattoni
Publisher: CRC Press
ISBN: 1420008412
Category : Psychology
Languages : en
Pages : 368

Book Description
A comprehensive, multidisciplinary review, Neural Plasticity and Memory: From Genes to Brain Imaging provides an in-depth, up-to-date analysis of the study of the neurobiology of memory. Leading specialists share their scientific experience in the field, covering a wide range of topics where molecular, genetic, behavioral, and brain imaging techniq

Studies of Gene Expression During Memory: I) Role of Extracellular Vesicles & Ii) Impact of Aging on Gene Expression in Mouse Hippocampus

Studies of Gene Expression During Memory: I) Role of Extracellular Vesicles & Ii) Impact of Aging on Gene Expression in Mouse Hippocampus PDF Author: Yang Tao
Publisher:
ISBN:
Category :
Languages : en
Pages : 99

Book Description
Learning and memory have long been hot topics in the field of neuroscience, not only because they play fundamental roles in human experience, but also because there are multiple diseases that are associated with deficits in learning and memory. At the cellular level, memory results from changes in the strength of the synaptic connections between neurons, and alterations in gene expression underly the persistence of many of these changes. Translation of synaptically localized mRNAs is important for long-term synaptic plasticity. Extracellular vesicles (EVs) contain RNAs and neuronal EV secretion has been reported to be regulated by synaptic activity, which leads to the hypothesis that EVs are transferred between cells in the nervous system and that mRNAs and microRNAs transferred through this pathway are important for local translation during neuronal plasticity. To test this hypothesis, we purified EVs from primary neuronal culture media and performed small RNA sequencing on neuronal evRNAs and their respective donor cells. We found an enrichment of small RNAs in EVs, and the composition of the small RNAs, including the miRNA profile, was distinct from that in donor cells. Our findings reveal a comprehensive map of RNAs inside neuronal EVs and identify multiple miRNAs as promising candidates for future investigation. Normal aging often involves some level of memory impairment and as such represents a physiologically relevant manipulation of plasticity and memory, with the comparison between young and aged mice providing insights into differences in gene regulation that may be central to plasticity and memory. We performed ATAC-seq and RNA-seq on the hippocampus of young and aged mice and found that aging resulted in significant changes in the expression of genes involved in neurogenesis, immune response, and cell adhesion, and in the alternative splicing of select myelin sheath genes. We found that aged female mice had higher levels of expression of several myelin sheath genes compared to aged male mice. Chromatin accessibility analysis revealed a more open chromatin structure in the hippocampus of aged animals compared to young animals, and many of these changes occurred at repetitive elements. However, changes in chromatin accessibility were not well-correlated with changes in gene expression. Our results provide insights into the changes in gene expression that occur with aging, highlighting changes in genes important for myelin sheath maintenance, and suggest that age-related chromatin accessibility changes may play an indirect role in age-related transcriptional changes.

Epigenetics, Brain and Behavior

Epigenetics, Brain and Behavior PDF Author: Paolo Sassone Corsi
Publisher: Springer Science & Business Media
ISBN: 3642279139
Category : Medical
Languages : en
Pages : 171

Book Description
Recent years have seen spectacular advances in the filed of epigenetics. These have attracted the interest of researchers in many fields and evidence connecting epigentic regulation to brain functions has been accumulationg. Neurons daily convert a variety of external stimuli into rapid or long-lasting changes in gene expression. A variety of studies have centered on the molcular mechanisms implicated in epigentic control and how these may operte in concert. It will be critical to unravel how specifity is achieved. The focus of this volume is on critical epigenetic regulation and chromatin remodeling events that occur in the nervous system and on the presumed mechanisms that operate within neurons to translate them into long-lasting neuronal responses.

Memory Reconsolidation

Memory Reconsolidation PDF Author: Satoshi Kida
Publisher: Elsevier Inc. Chapters
ISBN: 0128057912
Category : Psychology
Languages : en
Pages : 32

Book Description
Memory retrieval is not a passive phenomenon. Recent studies have shown that memory retrieval initiates two opposite and dissociable processes: memory reconsolidation and extinction. Reconsolidation acts to stabilize, whereas extinction tends to weaken, the expression of the original memory. This chapter reviews the regulation and mechanisms of reconsolidation and extinction and the current understanding of the relationship between the two.