The Striatal-Enriched Protein Tyrosine Phosphatase Gates Long-Term Potentiation and Fear Memory in the Lateral Amygdala

Paul, Surojit; Olausson, Peter; Venkitaramani, Deepa V.; Ручкина, И Н; Moran, Timothy D.; Tronson, Natalie C.; Mills, Evan; Hakim, Shawn; Salter, Michael W.; Taylor, Jane R.; Lombroso, Paul J.

doi:10.1016/j.biopsych.2006.08.005

Cited by 100 publications

(134 citation statements)

References 51 publications

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“…These results were due to the specificity of tone-shock pairings, as the control experiment (Figure 3a) showed that only the peak of activation in the 'paired' group was significantly higher than the Box ctrl group. In contrast with Paul et al (2007), who found in the rat a second peak of activation at 5 min after fear conditioning, even higher than the one at 60 min, we could not find any evidence for this second peak of phospho-activated labeled cells in the mouse (Figure 2b). As reviewed in Whishaw et al (2001), several comparative studies already described anatomical and behavioral differences between the mouse and the rat in their performance in various behavioral tests.…”

Section: The Time Course Of Erk/mapk Activation In the La Of The Mouscontrasting

confidence: 99%

“…Our analysis could reveal that there was indeed a difference between the rat and the mouse in the peaks of pMAPK in LA. Consistent with the results shown in rats (Paul et al, 2007;Schafe et al, 2000), there was a peak in the number of phospho-labeled cells at 60 min after fear conditioning, which went down again to basal levels by 180 min (Figure 2b). These results were due to the specificity of tone-shock pairings, as the control experiment (Figure 3a) showed that only the peak of activation in the 'paired' group was significantly higher than the Box ctrl group.…”

Section: The Time Course Of Erk/mapk Activation In the La Of The Moussupporting

confidence: 90%

“…Consequently, experimental procedures have to be adapted to analyze behavioral responses in these two species. Indeed, there are several differences in the conditioning protocols used by Paul et al (2007) in comparison with our study. In particular, the number of tone/shock presentations, intensity, and duration of the footshocks as well as tone frequency and intensity differed.…”

Section: The Time Course Of Erk/mapk Activation In the La Of The Mousmentioning

confidence: 62%

“…Thus, the tone acquires the ability to elicit a variety of behaviors indicative of fear and anxiety. Using these procedures, the amygdala has been identified as an essential structure in the neural circuit for conditioned fear and some molecular events in this region which contribute to conditioned fear (Bauer et al, 2002;Paul et al, 2007;Rattiner et al, 2004;Schafe et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Activation of ERK/MAPK in the Lateral Amygdala of the Mouse is Required for Acquisition of a Fear-Potentiated Startle response

Benedetto

Kallnik

Weisenhorn

et al. 2008

Neuropsychopharmacol

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There is considerable interest in examining the genes that may contribute to anxiety. We examined the function of ERK/MAPK in the acquisition of conditioned fear, as measured by fear-potentiated startle (FPS) in mice as a model for anticipatory anxiety in humans. We characterized the following for the first time in the mouse: (1) the expression of the ERK/MAPK signaling pathway components at the protein level in the lateral amygdala (LA); (2) the time course of activation of phospho-activated MAPK in the LA after fear conditioning; (3) if pharmacological inhibition of pMAPK could modulate the acquisition of FPS; (4) the cell-type specificity of pMAPK in the LA after fear conditioning. Using western blot and immunohistochemistry techniques and injecting the MEK inhibitor U0126 in the LA, we showed the following: (1) both MEK1/MEK2 and ERK1/ERK2 were co-expressed in the LA of the adult mouse brain; (2) there is a peak of pMAPK at 60 min after fear conditioning; (3) the ERK/MAPK signaling pathway activation is essential for the acquisition of an FPS response; (4) at 60 min, the pMAPK are exclusively neuronal and not glial. These results emphasize the importance of this signaling pathway in the acquisition of conditioned fear in the mouse. Given the widely held view that conditioned fear models the essential aspects of anxiety disorders, the results confirm the ERK/MAPK signaling pathway as a molecular target for the treatment of anxiety disorders in the clinic.

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Section: The Time Course Of Erk/mapk Activation In the La Of The Mouscontrasting

confidence: 99%

Section: The Time Course Of Erk/mapk Activation In the La Of The Moussupporting

confidence: 90%

Section: The Time Course Of Erk/mapk Activation In the La Of The Mousmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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Activation of ERK/MAPK in the Lateral Amygdala of the Mouse is Required for Acquisition of a Fear-Potentiated Startle response

Benedetto

Kallnik

Weisenhorn

et al. 2008

Neuropsychopharmacol

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“…PTSD has been associated with persisting changes in the amygdala's capacity for long-term potentiation (LTP) (Koshibu et al, 2011;Paul et al, 2007;Post et al, 1998), and LTP itself serves as a mediator of learned fear (Rogan et al, 1997). DNMT inhibitors disrupt hippocampal LTP Monsey et al, 2011), and recent studies confirmed the ability of DNMT inhibitors to affect synaptic function in the lateral amygdala (Monsey et al, 2011).…”

Section: Epigenetic Regulation Of Synaptic Plasticity In Ptsdmentioning

confidence: 99%

Epigenetic Mechanisms in Learned Fear: Implications for PTSD

Zovkic

Sweatt

2012

Neuropsychopharmacol

172

111

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One of the most exciting discoveries in the learning and memory field in the past two decades is the observation that active regulation of gene expression is necessary for experience to trigger lasting functional and behavioral change, in a wide variety of species, including humans. Thus, as opposed to the traditional view of 'nature' (genes) being separate from 'nurture' (environment and experience), it is now clear that experience actively drives alterations in central nervous system (CNS) gene expression in an ongoing fashion, and that the resulting transcriptional changes are necessary for experience to trigger altered long-term behavior. In parallel over the past decade, epigenetic mechanisms, including regulation of chromatin structure and DNA methylation, have been shown to be potent regulators of gene transcription in the CNS. In this review, we describe data supporting the hypothesis that epigenetic molecular mechanisms, especially DNA methylation and demethylation, drive long-term behavioral change through active regulation of gene transcription in the CNS. Specifically, we propose that epigenetic molecular mechanisms underlie the formation and stabilization of context-and cue-triggered fear conditioning based in the hippocampus and amygdala, a conclusion reached in a wide variety of studies using laboratory animals. Given the relevance of cued and contextual fear conditioning to post-traumatic stress, by extension we propose that these mechanisms may contribute to post-traumatic stress disorder (PTSD) in humans. Moreover, we speculate that epigenetically based pharmacotherapy may provide a new avenue of drug treatment for PTSD-related cognitive and behavioral function.

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Tyrosine phosphatase STEP₆₁ negatively regulates amyloid β‐mediated ERK/CREB signaling pathways via α7 nicotinic acetylcholine receptors

Zhang

Xie

Yang

et al. 2013

J of Neuroscience Research

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Striatal-enriched phosphatase 61 (STEP61 ) plays an essential role in synaptic plasticity and has recently been implicated in neurodegenerative disease. Here we characterized a possible role of STEP61 in Alzheimer's disease (AD) pathology using a mouse model of AD (Tg-APPswe/PSEN1dE9, APP/PS1 mice) and an in vitro model of AD [cortical neurons treated with amyloid β (Aβ)1-42 peptides]. Our data indicate age-related elevation of STEP61 levels and the proportion of dephosphorylated STEP61 (active STEP61 ) in wild-type mice, which was enhanced in APP/PS1 mice. Furthermore, the increased STEP61 levels and active STEP61 were observed in the hippocampus and cortex from 12-month-old APP/PS1 mice and in Aβ1-42 -treated cortical neurons. An α7 nicotinic acetylcholine receptors (nAChRs) antagonist, α-bungarotoxin (BTX), inhibited the Aβ1-42 -induced increase of STEP61 expression and activation. In addition, extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element binding (CREB) were impaired in Aβ1-42 -treated cortical neurons, and knockdown of STEP61 enhanced the activation of ERK1/2 and CREB. Collectively, these findings indicate two alternate pathological pathways effecting STEP61 regulation in AD. First, Aβ regulating STEP61 activity is mediated by Aβ binding to α7 nAChRs. Second, STEP61 negatively regulates Aβ-mediated ERK/CREB pathway, an important signaling cascade involved in memory formation.

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The Striatal-Enriched Protein Tyrosine Phosphatase Gates Long-Term Potentiation and Fear Memory in the Lateral Amygdala

Cited by 100 publications

References 51 publications

Activation of ERK/MAPK in the Lateral Amygdala of the Mouse is Required for Acquisition of a Fear-Potentiated Startle response

Activation of ERK/MAPK in the Lateral Amygdala of the Mouse is Required for Acquisition of a Fear-Potentiated Startle response

Epigenetic Mechanisms in Learned Fear: Implications for PTSD

Tyrosine phosphatase STEP₆₁ negatively regulates amyloid β‐mediated ERK/CREB signaling pathways via α7 nicotinic acetylcholine receptors

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The Striatal-Enriched Protein Tyrosine Phosphatase Gates Long-Term Potentiation and Fear Memory in the Lateral Amygdala

Cited by 100 publications

References 51 publications

Activation of ERK/MAPK in the Lateral Amygdala of the Mouse is Required for Acquisition of a Fear-Potentiated Startle response

Activation of ERK/MAPK in the Lateral Amygdala of the Mouse is Required for Acquisition of a Fear-Potentiated Startle response

Epigenetic Mechanisms in Learned Fear: Implications for PTSD

Tyrosine phosphatase STEP61 negatively regulates amyloid β‐mediated ERK/CREB signaling pathways via α7 nicotinic acetylcholine receptors

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Product

Resources

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Tyrosine phosphatase STEP₆₁ negatively regulates amyloid β‐mediated ERK/CREB signaling pathways via α7 nicotinic acetylcholine receptors