Krox20 may play a key role in the stabilization of long-term potentiation

Williams, Joanna M.; Dragunow, Mike; Lawlor, P.; Mason, S.E.; Abraham, Wickliffe C.; Leah, J.D.; Bravo, Rodrigo; Demmer, Jerome; Tate, Warren P.

doi:10.1016/0169-328x(94)00187-j

Cited by 95 publications

(52 citation statements)

References 26 publications

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“…67 and is involved, together with homer and BDNF, in the stabilization of long-term potentiation (LTP). [68][69][70] Interestingly, Krox20 expression is upregulated exclusively during the dark phase in the cortex and Hippo of rats exposed to an enriched environment. 71 The activity and neurotransmitter-induced early gene protein 4 (Ania-4) shares high homology with doublecortin-like kinase, CaM-Kinase, the CaMKrelated peptide (CARP) and the candidate plasticity gene 16 (CPG16), a protein serine/threonine kinase.…”

Section: Number Of Transcripts Affected By Single and Multiple Treatmmentioning

confidence: 98%

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

et al. 2006

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The significant proportion of depressed patients that are resistant to monoaminergic drug therapy and the slow onset of therapeutic effects of the selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake inhibitors (SNRIs) are two major reasons for the sustained search for new antidepressants. In an attempt to identify common underlying mechanisms for fast-and slow-acting antidepressant modalities, we have examined the transcriptional changes in seven different brain regions of the rat brain induced by three clinically effective antidepressant treatments: electro convulsive therapy (ECT), sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset antidepressant. Each of these antidepressant treatments was applied with the same regimen known to have clinical efficacy: 2 days of ECT (four sessions per day), 24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional changes were evaluated on RNA extracted from seven different brain regions using the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated using in situ hybridization or autoradiography for selected genes. The major findings of the study are:1. The transcriptional changes induced by SD, ECT and SSRI display a regionally specific distribution distinct to each treatment. 2. The fast-onset, short-lived antidepressant treatments ECT and SD evoked transcriptional changes primarily in the catecholaminergic system, whereas the slow-onset antidepressant FLX treatment evoked transcriptional changes in the serotonergic system. 3. ECT and SD affect in a similar manner the same brain regions, primarily the locus coeruleus, whereas the effects of FLX were primarily in the dorsal raphe and hypothalamus, suggesting that both different regions and pathways account for fast onset but short lasting effects as compared to slow-onset but long-lasting effects. However, the similarity between effects of ECT and SD is somewhat confounded by the fact that the two treatments appear to regulate a number of transcripts in an opposite manner. 4. Multiple transcripts (e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoidregulated kinase (Sgk1)), whose level was reported to be affected by antidepressants or behavioral manipulations, were also found to be regulated by the treatments used in the present study. Several novel findings of transcriptional regulation upon one, two or all three treatments were made, for the latter we highlight homer, erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1), glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5. Transcripts encoding proteins involved in synaptic plasticity in the hippocampus were strongly affected by ECT and SD, but not by FLX.The novel transcripts, concomitantly regulated by several antidepressant treatments, may represent novel targets for fast onset, long-duration antidepressants.

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Section: Number Of Transcripts Affected By Single and Multiple Treatmmentioning

confidence: 98%

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

et al. 2006

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“…Egr-2 expression was shown to be robustly and sustainedly induced in the dentate gyrus following LTP-inducing perforant path stimulation suggesting that egr-2 plays a role in the maintenance of LTP (Williams et al, 1995). However, a role of egr-2 in memory-related or other cognitive functions remains to be established.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task

DeSteno

Schmauss

2008

Neuroscience

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Early growth response (egr) genes encode transcription factors that are induced by stimuli that cause synaptic plasticity. Here we show that the expression of one member of this family, egr-2, is induced in the orbital frontal cortex (OFC) and medial prefrontal cortex (mPFC) of mice performing an attention-set-shifting task (ASST). The ASST is a series of two-choice perceptual discriminations between different odors and textures. Within the OFC and mPFC, different subregions exhibited egr-2 induction in response to different test-related features. In the medial OFC and the anterior cingulate subregion of the mPFC, egr-2 induction occurred in response to exposure to the novel odor stimulus. In the ventrolateral OFC and the pre-and infralimbic mPFC, additional egr-2 induction occurred during the associative learning phase of the ASST. In the infralimbic mPFC, further egr-2 induction occurred when mice performed set-shifting and reversal learning phases of the ASST. Mice with enhanced set-shifting performance exhibited decreased egr-2 induction in the mPFC indicating that the magnitude of egr-2 induction correlates with the magnitude of attentional demand. This decrease was largest in the infralimbic mPFC suggesting further that egr-2 induction in this region plays a role in the attentional control during set-shifting.In contrast to egr-2, neither egr-1 nor egr-3 expression was altered in ASST-tested mice, and no egr-2 induction occurred in mice that performed a spatial working memory task. These findings suggest a specific role of egr-2-mediated transcriptional activation in cognitive functions associated with attention. Keywordsearly growth response gene; medial prefrontal cortex; orbital frontal cortex; attention; working memory; miceThe earliest genomic response to synaptic activity is the induction of expression of immediate early genes (IEGs) encoding transcription factors that participate in synaptic and structural neuronal responses to external stimulation. Although induction of expression of the IEG c- ., Email address: cs581@columbia.edu (C. Schmauss). Section Editor: Dr. Werner Sieghart (Molecular Neuroscience) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 April 21. Published in final edited form as:Neuroscience. 2008 March 18; 152(2): 417-428. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscriptfos is a powerful tool to map the activation of neuronal pathways (Sagar et al, 1988), the identification of other IEG transcription factors is critical...

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“…Among the many IEGs of the Fos, Jun, or Egr family that are turned on after LTP, Zif268 has attracted much attention because its transcription is reliably associated with the expression of the protein synthesis-dependent late phase of LTP in anesthetized and awake rats and appears to correlate with the persistence of LTP (Abraham et al, 1991(Abraham et al, , 1993Richardson et al, 1992;Worley et al, 1993;Dragunow, 1996). In addition to the expression of Zif268, other members of the Erg family, such as Krox-20 and Egr-3, are also upregulated after LTP in the dentate gyrus (Yamagata et al, 1994;Williams et al, 1995). Recently, analysis of Zif268 DNA binding activity using gel-shift assays showed that the increase in Zif268 protein after induction of LTP is associated with increased binding of the protein to its response element (Williams et al, 2000).…”

Section: Regulated Transcription Of Zif268 In Synaptic Plasticity Andmentioning

confidence: 99%

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

2002

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ABSTRACT:The immediate-early gene Zif268 is a member of the Egr family of inducible transcription factors. Data from gene expression studies have suggested that this gene may play a critical role in initial triggering of the genetic machinery that has long been considered a necessary mechanism for maintenance of the later phases of LTP and also for the consolidation or stabilization of long-lasting memories. Until recently, however, the data supporting this assumption have been based primarily on circumstantial evidence, with no direct evidence to suggest that Zif268 is required for long-lasting synaptic plasticity and memory. In this report, we review our own data using Zif268 mutant mice; we show that although the early phase of dentate gyrus LTP is normal in these mice, the later phases are not present, and the ability of the mice to maintain learned information over a 24-h period is deficient. In addition, we present new information showing a task-dependent gene dosage effect in Zif268 heterozygous mice. We show that spatial learning is particularly sensitive to reduced levels of Zif268, as one-half of the complement of Zif268 in heterozygous mice is insufficient to maintain spatial long-term memories.

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Krox20 may play a key role in the stabilization of long-term potentiation

Cited by 95 publications

References 26 publications

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task

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

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