Fear learning transiently impairs hippocampal cell proliferation

Pham, Kara; McEwen, Bruce S.; LeDoux, Joseph E.; Nader, Karim

doi:10.1016/j.neuroscience.2004.09.015

Cited by 76 publications

(58 citation statements)

References 32 publications

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“…In addition, blocking hippocampal neurogenesis has no effect on consolidation of context conditioning (Shors et al, 2002). Accordingly, Pham et al (2005) showed that context conditioning caused a moderate attenuation of neurogenesis in the dentate gyrus. Together, these results suggest that the amnesic effects of ara-C are related to its potential effects on gene expression regulation via blockade of DNA recombination processes and not to blockade of DNA replication and thereby neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…The fact that the effects of ara-CTP on CTA consolidation were observed as early as 4 h after training suggested that its effects were related to blockade of DNA recombination, rather than replication and neurogenesis (Wang et al, 2003). Here, we questioned whether recombination processes sensitive to ara-CTP are involved in the consolidation of context fear conditioning, a task that is independent of neurogenesis (Shors et al, 2002;Pham et al, 2005). The data show that ara-C specifically impaired consolidation, without interfering with reconsolidation of context fear memory.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Inhibitor of DNA Recombination Blocks Memory Consolidation, But Not Reconsolidation, in Context Fear Conditioning

Colón-Cesario¹,

Wang²,

Ramos³

et al. 2006

J. Neurosci.

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Genomic recombination requires cutting, processing, and rejoining of DNA by endonucleases, polymerases, and ligases, among other factors. We have proposed that DNA recombination mechanisms may contribute to long-term memory (LTM) formation in the brain. Our previous studies with the nucleoside analog 1-␤-D-arabinofuranosylcytosine triphosphate (ara-CTP), a known inhibitor of DNA ligases and polymerases, showed that this agent blocked consolidation of conditioned taste aversion without interfering with short-term memory (STM). However, because polymerases and ligases are also essential for DNA replication, it remained unclear whether the effects of this drug on consolidation were attributable to interference with DNA recombination or neurogenesis. Here we show, using C57BL/6 mice, that ara-CTP specifically blocks consolidation but not STM of context fear conditioning, a task previously shown not to require neurogenesis. The effects of a single systemic dose of cytosine arabinoside (ara-C) on LTM were evident as early as 6 h after training. In addition, although ara-C impaired LTM, it did not impair general locomotor activity nor induce brain neurotoxicity. Importantly, hippocampal, but not insular cortex, infusions of ara-C also blocked consolidation of context fear conditioning. Separate studies revealed that context fear conditioning training significantly induced nonhomologous DNA end joining activity indicative of DNA ligasedependent recombination in hippocampal, but not cortex, protein extracts. Finally, unlike inhibition of protein synthesis, systemic ara-C did not block reconsolidation of context fear conditioning. Our results support the idea that DNA recombination is a process specific to consolidation that is not involved in the postreactivation editing of memories.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Inhibitor of DNA Recombination Blocks Memory Consolidation, But Not Reconsolidation, in Context Fear Conditioning

Colón-Cesario¹,

Wang²,

Ramos³

et al. 2006

J. Neurosci.

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show abstract

“…In contrast to the studies demonstrating a stimulatory effect of learning on adult neurogenesis, there are also reports that training on various learning tasks either does not alter the number of new neurons in the hippocampus (van Praag et al, 1999;Snyder et al, 2005;Van der Borght et al, 2005a) or actually decreases it (Dobrossy et al, 2003;Ambrogini et al, 2004a;Olairu et al, 2005;Pham et al, 2005). There are several possible reasons for these discrepant findings.…”

Section: Evidence Againstmentioning

confidence: 96%

Is there a link between adult neurogenesis and learning?

2006

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During the past several years, evidence has accumulated suggesting a relationship between newly born cells in the hippocampus and various types of learning and memory. However, most of the evidence is correlational and some of it does not agree. This review discusses both sides of this issue, considering the effects of learning on the production of new neurons in the dentate gyrus and the question of whether newly born cells participate in learning and memory.

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“…Cell survival was later shown to be regulated by the acquisition and not memory expression (Anderson et al 2011), the sex of the animals (Dalla et al 2009), and the degree of task difficulty. Indeed, establishing a contextual conditioned stimulus representation acquired in a single training trial is not sufficient to change the survival of cells born 10 d before exposure to the task (Pham et al 2005).…”

Section: Effect On Cell Numbersmentioning

confidence: 99%

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

Abrous

Wojtowicz

2015

Cold Spring Harb Perspect Biol

102

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During the last decade, the questions on the functionality of adult neurogenesis have changed their emphasis from if to how the adult-born neurons participate in a variety of memory processes. The emerging answers are complex because we are overwhelmed by a variety of behavioral tasks that apparently require new neurons to be performed optimally. With few exceptions, the hippocampal memory system seems to use the newly generated neurons for multiple roles. Adult neurogenesis has given the dentate gyrus new capabilities not previously thought possible within the scope of traditional synaptic plasticity. Looking at these new developments from the perspective of past discoveries, the science of adult neurogenesis has emerged from its initial phase of being, first, a surprising oddity and, later, exciting possibility, to the present state of being an integral part of mainstream neuroscience. The answers to many remaining questions regarding adult neurogenesis will come along only with our growing understanding of the functionality of the brain as a whole. This, in turn, will require integration of multiple levels of organization from molecules and cells to circuits and systems, ultimately resulting in comprehension of behavioral outcomes.

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Fear learning transiently impairs hippocampal cell proliferation

Cited by 76 publications

References 32 publications

An Inhibitor of DNA Recombination Blocks Memory Consolidation, But Not Reconsolidation, in Context Fear Conditioning

An Inhibitor of DNA Recombination Blocks Memory Consolidation, But Not Reconsolidation, in Context Fear Conditioning

Is there a link between adult neurogenesis and learning?

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

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