Regulated transcription of the immediate‐early gene <i>Zif268</i>: Mechanisms and gene dosage‐dependent function in synaptic plasticity and memory formation

Bozon, Bruno; Davis, Sabrina; Laroche, Serge

doi:10.1002/hipo.10100

Cited by 154 publications

(134 citation statements)

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“…Interestingly, in previous experiments we showed that half the complement of Zif268 in heterozygous mutant mice is not sufficient to allow the formation of a memory for the spatial location of objects as heterozygous mice are impaired in this task, however it is sufficient to form a memory of the nature of the objects [15]. Mirroring this, overexpression of Zif268 leads to enhancement of the more demanding memory for the spatial location of objects, but not to improvement of object memory over and above that observed in WT mice.…”

Section: Discussionmentioning

confidence: 90%

“…To determine the effect of Zif268 overexpression on recognition memory, we first evaluated performance in an object recognition memory task using standardized procedures as previously described [1,15]. Briefly, the experimental apparatus was a black plastic square open field arena (45 Â 45 Â 30 cm) with wood shavings on the floor and a cue card placed at a fixed location on the top of one of the walls of the open field to facilitate spatial mapping.…”

Section: Zif268 Overexpression Facilitates Memory Of the Spatial Locamentioning

confidence: 99%

“…We then assessed the performance of WT and Zif268-overexpressing mice in an object -place recognition memory task following procedures described previously [15,18]. In this task, three different objects were present during training (consisting of two 10-min sessions with a 10-min interval) and during the test conducted 30 min, 1 day or 3 days after training, the spatial position of one of the objects was changed, in a counterbalanced manner among individuals, to a new spatial location.…”

Section: Zif268 Overexpression Facilitates Memory Of the Spatial Locamentioning

confidence: 99%

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Zif268 / Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory

Penke

Morice

Veyrac

et al. 2014

Phil. Trans. R. Soc. B

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It is well established that Zif268/Egr1 , a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of Zif268 in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce Zif268 overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that Zif268 overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging Zif268 contribute to determining the strength of newly encoded memories.

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Section: Discussionmentioning

confidence: 90%

Section: Zif268 Overexpression Facilitates Memory Of the Spatial Locamentioning

confidence: 99%

Section: Zif268 Overexpression Facilitates Memory Of the Spatial Locamentioning

confidence: 99%

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Zif268 / Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory

Penke

Morice

Veyrac

et al. 2014

Phil. Trans. R. Soc. B

Self Cite

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“…Current consolidation theory posits that a series of cellular and molecular processes within the MTL are needed during and immediately after learning to store a persistent memory trace. The formation of the trace is a dynamic process involving posttranslational protein modification and changes in gene expression (3)(4)(5)21). These events culminate in modifications in the number and strength of synaptic connections (9) that might represent the structural trace of the memory engram [reviewed by Lamprecht and LeDoux (2)].…”

Section: Discussionmentioning

confidence: 99%

“…These begin with neurotransmitter receptor activation that induces shortterm changes in synaptic efficacy based on receptor phosphorylation and trafficking (3,4). Subsequently, alterations in gene expression and protein synthesis occur that are the basis for longterm structural modifications (5,6).…”

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confidence: 99%

Ventral striatal plasticity and spatial memory

Ferretti

Roullet

Sargolini

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Spatial memory formation is a dynamic process requiring a series of cellular and molecular steps, such as gene expression and protein translation, leading to morphological changes that have been envisaged as the structural bases for the engram. Despite the role suggested for medial temporal lobe plasticity in spatial memory, recent behavioral observations implicate specific components of the striatal complex in spatial information processing. However, the potential occurrence of neural plasticity within this structure after spatial learning has never been investigated. In this study we demonstrate that blockade of cAMP response element binding protein-induced transcription or inhibition of protein synthesis or extracellular proteolytic activity in the ventral striatum impairs longterm spatial memory. These findings demonstrate that, in the ventral striatum, similarly to what happens in the hippocampus, several key molecular events crucial for the expression of neural plasticity are required in the early stages of spatial memory formation. T he formation of long-term memories is believed to involve a dynamic process by which a labile memory is progressively converted into a more stable and potentially permanent trace. Evidence for such a time-dependent process comes from studies demonstrating that electroconvulsive shock produces amnesia only if delivered shortly after learning, whereas the same treatment is ineffective when delivered several hours later (1). Long-term memory is accompanied by changes in neuronal morphology and connectivity, and these alterations are thought to be essential for the stabile encoding of new information (2). This transformation has been suggested to depend upon plastic changes that involve a sequence of specific and coordinated cellular processes. These begin with neurotransmitter receptor activation that induces shortterm changes in synaptic efficacy based on receptor phosphorylation and trafficking (3, 4). Subsequently, alterations in gene expression and protein synthesis occur that are the basis for longterm structural modifications (5, 6).A key issue in the study of memory in vertebrates is the brain site at which these processes occur. Clinical evidence in humans suggests that structures within the medial temporal lobe (MTL) play a prominent role in long-term memories. MTL lesions induce profound deficits in the formation of long-lasting declarative memories while sparing the acquisition of nondeclarative memories such as visual-motor skills (7,8). Such findings suggest that the hippocampus might be an essential site where plasticity occurs in the initial steps of declarative memory stabilization. Accordingly, those molecular events thought to be crucial for the long-term encoding of memories such as regulation of gene expression and protein synthesis, as well as structural changes, have been described in the hippocampus after spatial learning (6, 9, 10).Recent experimental evidence, however, demonstrates that structures different from the hippocampus might also be involved in ...

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Regulation of classical zinc fingers for neuronal signaling in the central nervous system

Hwang,

Park,

Kim

et al. 2024

Bulletin Korean Chem Soc

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Zinc finger (ZF) proteins are well‐known for their regulatory functions in the central dogma, and their structural domains serve as promising scaffolds for the study of neurodegenerative diseases. These proteins often contain multiple ZF domains, enabling interactions with target molecules that regulate transcription and translation. The Cys2His2 (C2H2) type ZF domains, found in the brain, are associated with long‐ and short‐term memory, neuronal differentiation and development, and other physiological processes. The classical C‐X2‐C‐X12‐H‐X3‐H type ZF domains have been detected in studies of Parkinson's disease (PD) and are closely linked to biological pathways involved in a wide range of neurodegenerative diseases. In this review, we introduce three ZF proteins expressed in the brain: Parkin‐interacting substrate (PARIS), zinc finger and BTB domain‐containing 20 (ZBTB20), and zinc finger protein 18 (ZNF18). We explore the structural and functional roles of these ZF proteins in the brain. Each of these proteins contains more than four ZF domains, as well as functional domains such as KRAB, BTB, and SCAN, which perform modular roles independently of the ZF domains. Biophysical studies of PARIS have demonstrated that its classical three‐ZF domain, PARIS(ZF2–4), forms hydrogen bonds with insulin response sequences (IRSs) with high specificity (Kd = 38.9 ± 2.4 nM). Metal coordination studies showed that PARIS binds Co2+ with high affinity (Kd = 49.1 ± 7.7 nM), more strongly than other ZF domains, and it also coordinates with other xenobiotic metal ions such as Fe2+ and Ni2+. Although Zn2+–PARIS(ZF2–4) binds specifically to IRSs, Fe2+–, Fe3+– or Co2+–PARIS(ZF2–4) cannot, due to distortions in the ZF domain structure that disrupt hydrogen bonding. These brain‐specific ZF domains exhibit common patterns, with similar numbers of ZF domains and sequence homology at the C‐terminus, whereas both the ZF domains and N‐terminal protein–protein interaction domains contribute to their functional versatility. Elucidating the structure and function of these classical ZF proteins offers promising avenues for the treatment of diverse brain disorders, including Alzheimer's disease, PD, and autism spectrum disorder.

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Regulated transcription of the immediate‐early gene Zif268: Mechanisms and gene dosage‐dependent function in synaptic plasticity and memory formation

Cited by 154 publications

References 92 publications

Zif268 / Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory

Zif268 / Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory

Ventral striatal plasticity and spatial memory

Regulation of classical zinc fingers for neuronal signaling in the central nervous system

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