Differential expression of immediate early genes in the hippocampus and spinal cord

Wisden, William; Er̀rington, M.L.; Williams, Simon; Dunnett, Stephen B.; Waters, Catherine; Hitchcock, Daniel F. A.; Evan, Gérard I.; Bliss, T. V. P.; Hunt, Stephen P.

doi:10.1016/0896-6273(90)90118-y

Cited by 658 publications

(309 citation statements)

References 49 publications

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“…The longer-lasting phases of LTP require the transcription of genes and the synthesis of proteins during a critical period (Otani et al, 1989;Nguyen et al, 1994;Frey and Morris, 1997). Within the first few hours of LTP, there is activation of specific immediate early genes (IEGs) (Cole et al, 1989;Wisden et al, 1990) encoding transcription factors that interact with promoter regulatory elements of a host of downstream effector genes. A crucial event in signal transduction leading to gene regulation in neurons is the activation of protein kinases.…”

Section: Abstract: Hippocampus; Ltp; Mapk/erk; Elk-1 Phosphorylationmentioning

confidence: 99%

The MAPK/ERK Cascade Targets Both Elk-1 and cAMP Response Element-Binding Protein to Control Long-Term Potentiation-Dependent Gene Expression in the Dentate GyrusIn Vivo

et al. 2000

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The mitogen-activated protein kinase/extracellular signalregulated kinase (MAPK/ERK) signaling cascade contributes to synaptic plasticity and to long-term memory formation, yet whether MAPK/ERK controls activity-dependent gene expression critical for long-lasting changes at the synapse and what the events underlying transduction of the signal are remain uncertain. Here we show that induction of long-term potentiation (LTP) in the dentate gyrus in vivo leads to rapid phosphorylation and nuclear translocation of MAPK/ERK. Following a similar time course, the two downstream transcriptional targets of MAPK/ERK, cAMP response element-binding protein (CREB) and the ternary complex factor Elk-1, a key transcriptionalregulator of serum response element (SRE)-driven gene expression, were hyperphosphorylated and the immediate early gene zif268 was upregulated. The mRNA encoding MAP kinase phosphatase MKP-1 was upregulated at the time point when MAPK/ERK phosphorylation had returned to basal levels, suggesting a negative feedback loop to regulate deactivation of MAPK/ERK. We also show that inhibition of the MAPK/ERK cascade by the MAPK kinase MEK inhibitor SL327 prevented CREB and Elk-1 phosphorylation, and LTP-dependent gene induction, resulting in rapidly decaying LTP. In conclusion, we suggest that Elk-1 forms an important link in the MAP kinase pathway to transduce signals from the cell surface to the nucleus to activate the genetic machinery necessary for the maintenance of synaptic plasticity in the dentate gyrus. Thus, MAPK/ERK activation is required for LTP-dependent transcriptional regulation and we suggest this is regulated by two parallel signaling pathways, the MAPK/ERK-Elk-1 pathway targeting SRE and the MAPK/ERK-CREB pathway targeting CRE.

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Section: Abstract: Hippocampus; Ltp; Mapk/erk; Elk-1 Phosphorylationmentioning

confidence: 99%

The MAPK/ERK Cascade Targets Both Elk-1 and cAMP Response Element-Binding Protein to Control Long-Term Potentiation-Dependent Gene Expression in the Dentate GyrusIn Vivo

et al. 2000

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“…for transcriptional regulation by the excitatory neurotransmitter glutamate (Cole et al, 1989;Wisden et al, 1990;Lerea et al, 1992;Bading et al, 1993Bading et al, , 1995Lerea and McNamara, 1993). A previous study has shown that the c-fos SRE can f unction as an NMDA receptor-responsive element (Bading et al, 1993).…”

Section: Nmda Receptor Activation Can Mediate Transcriptional Inductimentioning

confidence: 99%

“…In contrast, SRE-dependent transcription (discussed below) can be stimulated independently of increases in nuclear calcium by a rise in cytoplasmic calcium (Hardingham et al, 1997). This may explain why the zif/268 gene, which contains several SREs in its promoter (Changelian et al, 1989;Christy et al, 1989), is activated even with moderate LTP-inducing stimuli that may not increase the nuclear calcium concentration (Cole et al, 1989;Wisden et al, 1990;Worley et al, 1993). The molecular mechanisms controlled by nuclear calcium may involve CaM kinase IV.…”

Section: Cre-mediated Calcium-activated Transcriptionmentioning

confidence: 99%

Calcium Controls Gene Expression via Three Distinct Pathways That Can Function Independently of the Ras/Mitogen-Activated Protein Kinases (ERKs) Signaling Cascade

et al. 1997

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Calcium ions are the principal second messenger in the control of gene expression by electrical activation of neurons. However, the full complexity of calcium-signaling pathways leading to transcriptional activation and the cellular machinery involved are not known. Using the c-fos gene as a model system, we show here that the activity of its complex promoter is controlled by three independently operating signaling mechanisms and that their functional significance is cell type-dependent. The serum response element (SRE), which is composed of a ternary complex factor (TCF) and a serum response factor (SRF) binding site, integrates two calcium-signaling pathways. In PC12 cells, calcium-regulated transcription mediated by the SRE requires the TCF site and is not inhibited by expression of the dominant-negative Ras mutant, RasN17, nor by the MAP kinase kinase 1 inhibitor PD 98059. In contrast, TCF-dependent transcriptional regulation by nerve growth factor or epidermal growth factor is mediated by a Ras/MAP kinases (ERKs) pathway targeting the TCF Elk-1. In AtT20 cells and hippocampal neurons, calcium signals can stimulate transcription via a TCFindependent mechanism that requires the SRF binding site. The cyclic AMP response element (CRE), which cooperates with the TCF site in growth factor-regulated transcription, is a target of a third calcium-regulated pathway that is little affected by the expression of RasN17 or by PD 98059. Thus, calcium can stimulate gene expression via a TCF-, SRF-, and CRE-linked pathway that can operate independently of the Ras/MAP kinases (ERKs) signaling cascade in a cell type-dependent manner.

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“…While it is now well established that long-term potentiation (LTP), a physiological model of the memory storage process, activates immediate early genes encoding transcription factors (1,2), there is no evidence to our knowledge indicating what target genes are activated by these transcription factors. GAP-43, ¶ the presynaptically localized, growth-associated protein whose expression is up-regulated during axonal outgrowth in development and axonal regeneration (3), and whose phosphorylation is increased after LTP (4), is one likely candidate target gene (see also ref.…”

mentioning

confidence: 99%

Long-term potentiation activates the GAP-43 promoter: Selective participation of hippocampal mossy cells

Namgung

Matsuyama

Routtenberg

1997

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

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Perforant path long-term potentiation (LTP) in intact mouse hippocampal dentate gyrus increased the neuron-specific, growth-associated protein GAP-43 mRNA in hilar cells 3 days after tetanus, but surprisingly not in granule cells While it is now well established that long-term potentiation (LTP), a physiological model of the memory storage process, activates immediate early genes encoding transcription factors (1, 2), there is no evidence to our knowledge indicating what target genes are activated by these transcription factors. GAP-43, ¶ the presynaptically localized, growth-associated protein whose expression is up-regulated during axonal outgrowth in development and axonal regeneration (3), and whose phosphorylation is increased after LTP (4), is one likely candidate target gene (see also ref. 5). A previous study of chronic recording in intact freely moving rats 3 days after LTP induction revealed that perforant path LTP altered GAP-43 mRNA expression (6). To explore the hypothesis that the alteration in GAP-43 mRNA was related to altered transcriptional activity of the GAP-43 gene in hippocampal neurons after LTP, we first studied the effect of LTP in the intact mouse on the endogenous pattern of GAP-43 mRNA transcript levels with in situ hybridization. We then studied the effect of LTP on promoter activation in transgenic mice bearing a GAP-43 promoter-lacZ reporter construct. MATERIALS AND METHODSAnimals. Mouse strain C57BL͞6 was obtained from The Jackson Laboratory. Heterozygous GAP-43͞lacZ transgenic mouse line 252 bearing 6-kb 5Ј-flanking and 11-kb first intron sequence driving lacZ reporter gene was bred with C57BL͞6 mice, and homozygous transgenic mice were initially screened by genomic DNA Southern or dot hybridization. Constitutive expression of the transgene in hippocampus in GAP-43͞lacZ transgenic mouse line 252 has been described (7, 8). Thirty-five male homozygous transgenic mice (2 months old) were used in the electrophysiological and histochemical analysis.Electrophysiology. In vivo LTP in anesthetized mice was performed essentially as described previously (9). Potentiated responses were measured by percent baseline population spike amplitude. Mean potentiation of combined 1-, 2-, and 3-day LTP group animals was 255% Ϯ 40.1% (n ϭ 20; mean Ϯ SEM) over the 2-hr recording session and did not show any significant difference from that of wild-type C57BL͞6 mice (229.4% Ϯ 36.3%, P Ͼ 0.10). Mean response of the low-frequency control (LFC) animals during the 2-hr recording period was 101.1 Ϯ 5.5 (n ϭ 15). In the LTP experiment with DL-aminophosphonovalerate (APV; Sigma) ejection, 80 nl (1.6 nmol) of APV dissolved in 20 mM Tris⅐HCl (pH 8.0) was pressure-ejected from the recording micropipette into the dentate gyrus molecular layer, using procedures described earlier (10). APV was delivered 15 min prior to high-frequency tetanic stimulation. Equivalent volumes of 20 mM Tris vehicle were ejected into the same region of the hippocampus in control group animals. Potentiated responses in the molecul...

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Differential expression of immediate early genes in the hippocampus and spinal cord

Cited by 658 publications

References 49 publications

The MAPK/ERK Cascade Targets Both Elk-1 and cAMP Response Element-Binding Protein to Control Long-Term Potentiation-Dependent Gene Expression in the Dentate GyrusIn Vivo

The MAPK/ERK Cascade Targets Both Elk-1 and cAMP Response Element-Binding Protein to Control Long-Term Potentiation-Dependent Gene Expression in the Dentate GyrusIn Vivo

Calcium Controls Gene Expression via Three Distinct Pathways That Can Function Independently of the Ras/Mitogen-Activated Protein Kinases (ERKs) Signaling Cascade

Long-term potentiation activates the GAP-43 promoter: Selective participation of hippocampal mossy cells

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