SnapShot: Local Protein Translation in Dendrites

Dieck, Susanne tom; Hanus, Cyril; Schuman, Erin M.

doi:10.1016/j.neuron.2014.02.009

Cited by 22 publications

(24 citation statements)

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“…We found that the effect of LY39 on NMDARs was effectively blocked by both mTOR inhibitor rapamycin and transcription inhibitor actinomycin-D. These findings are consistent with previous studies in which mTOR is found to mediate protein synthesis of NMDARs (Li et al 2010, Miller et al 2014), indicating the involvement of local protein synthesis (Gong et al, 2006; Hanus and Schuman, 2013; tom Dieck et al, 2014; Wang et al, 2013). To test this possibility, we examined the expression of 4E-BP1, an mRNA suppressor downstream of mTOR, and its phosphorylated form, p4E-BP1.…”

Section: Discussionsupporting

confidence: 92%

LY395756, an mGluR2 agonist and mGluR3 antagonist, enhances NMDA receptor expression and function in the normal adult rat prefrontal cortex, but fails to improve working memory and reverse MK801-induced working memory impairment

Yang

Xing

et al. 2015

Experimental Neurology

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Targeting group II metabotropic glutamate receptors (mGluR2/3) has been proposed to correct the dysfunctional glutamatergic system, particularly NMDA receptor (NMDAR) hypofunction, for treatment of schizophrenia. However, how activation of mGluR2/3 affects NMDAR function in adult animals remains elusive. Here we show the effects of LY395756 (LY39), a compound acting as both an mGluR2 agonist and mGluR3 antagonist, on the NMDAR expression and function of normal adult rat prefrontal cortex (PFC) as well as working memory function in the MK801 model of schizophrenia. We found that in vivo administration of LY39 significantly increased the total protein levels of NMDAR subunits and NR2B phosphorylation in the PFC, along with the amplitude of NMDAR-mediated miniature excitatory postsynaptic currents (mEPSC) in the prefrontal cortical neurons. Moreover, LY39 also significantly increased mTOR and pmTOR expression, but not ERK1/2, Akt, and GSK3β, suggesting an activation of mTOR signaling. Indeed, the mTOR inhibitor rapamycin, and actinomycin-D, a transcription inhibitor, blocked the enhanced effects of LY39 on NMDAR-mEPSCs. These results indicate that LY39 regulates NMDAR expression and function through unidentified mTOR-mediated protein synthesis in the normal adult rat PFC. However, this change is insufficient to affect working memory function in normal animals, nor to reverse the MK801-induced working memory deficit. Our data provide the first evidence of an in vivo effect of a novel compound that acts as both an mGluR2 agonist and mGluR3 antagonist on synaptic NMDAR expression and function in the adult rat PFC, although its effect on PFC-dependent cognitive function remains to be explored.

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Section: Discussionsupporting

confidence: 92%

LY395756, an mGluR2 agonist and mGluR3 antagonist, enhances NMDA receptor expression and function in the normal adult rat prefrontal cortex, but fails to improve working memory and reverse MK801-induced working memory impairment

Yang

Xing

et al. 2015

Experimental Neurology

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“…Enduring LTP also engages local protein synthesis at activated synapses (Bourne et al 2007b;Bramham 2008;Tom Dieck et al 2014). The mRNAs translated locally at potentiated synapses could come from at least three sources: mRNAs previously deposited in the spines, mRNAs that are transported into spines from the dendrites, and replenishment of these local stores of mRNA with transport of new mRNA from the soma.…”

Section: Discussionmentioning

confidence: 99%

Augmenting saturated LTP by broadly spaced episodes of theta-burst stimulation in hippocampal area CA1 of adult rats and mice

Cao

Harris

2014

Journal of Neurophysiology

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Cao G, Harris KM. Augmenting saturated LTP by broadly spaced episodes of theta-burst stimulation in hippocampal area CA1 of adult rats and mice. J Neurophysiol 112: 1916 -1924. First published July 23, 2014 doi:10.1152/jn.00297.2014.-Hippocampal long-term potentiation (LTP) is a model system for studying cellular mechanisms of learning and memory. Recent interest in mechanisms underlying the advantage of spaced over massed learning has prompted investigation into the effects of distributed episodes of LTP induction. The amount of LTP induced in hippocampal area CA1 by one train (1T) of theta-burst stimulation (TBS) in young Sprague-Dawley rats was further enhanced by additional bouts of 1T given at 1-h intervals. However, in young Long-Evans (LE) rats, 1T did not initially saturate LTP. Instead, a stronger LTP induction paradigm using eight trains of TBS (8T) induced saturated LTP in hippocampal slices from both young and adult LE rats as well as adult mice. The saturated LTP induced by 8T could be augmented by another episode of 8T following an interval of at least 90 min. The success rate across animals and slices in augmenting LTP by an additional episode of 8T increased significantly with longer intervals between the first and last episodes, ranging from 0% at 30-and 60-min intervals to 13-66% at 90-to 180-min intervals to 90 -100% at 240-min intervals. Augmentation above initially saturated LTP was blocked by the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). These findings suggest that the strength of induction and interval between episodes of TBS, as well as the strain and age of the animal, are important components in the augmentation of LTP. spaced learning; metaplasticity; memory; synaptic plasticity LONG-TERM POTENTIATION (LTP) is a persistent increase in synaptic strength, induced by brief high-frequency stimulation, that is widely accepted as a model for studying the cellular and molecular mechanisms of learning and memory (Bliss and Lomo 1973;Lynch et al. 1990). Some patterns of stimulation have no direct effect on synaptic strength but instead modulate the subsequent expression of long-term plasticity, a phenomenon known as metaplasticity (Abraham et al.

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“…; Perry & Fainzilber ; Tom Dieck et al . ). For such localized translation, the dendritic transport of mRNAs is a prerequisite, and the cis‐acting elements required for localization are often reside in 3′ UTR of mRNAs (Kobayashi et al .…”

Section: Introductionmentioning

confidence: 97%

Dendritic transport element of human arc mRNA confers RNA degradation activity in a translation‐dependent manner

2016

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Localization of mRNA in neuronal cells is a critical process for spatiotemporal regulation of gene expression. Cytoplasmic localization of mRNA is often conferred by transport elements in 3 0 untranslated region (UTR). Activity-regulated cytoskeleton-associated protein (arc) mRNA is one of the localizing mRNAs in neuronal cells, and its localization is mediated by dendritic targeting element (DTE). As arc mRNA has introns in its 3 0 UTR, it was thought that arc mRNA is a natural target of nonsense-mediated mRNA decay (NMD). Here, we show that DTE in human arc 3 0 UTR has destabilizing activity of RNA independent of NMD pathway. DTE alone was able to cause instability of the reporter mRNA and this degradation was dependent on translation. Our results indicate that DTE has dual activity in mRNA transport and degradation, which suggests the novel spatiotemporal regulation mechanism of activitydependent degradation of the mRNA.

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SnapShot: Local Protein Translation in Dendrites

Cited by 22 publications

References 0 publications

LY395756, an mGluR2 agonist and mGluR3 antagonist, enhances NMDA receptor expression and function in the normal adult rat prefrontal cortex, but fails to improve working memory and reverse MK801-induced working memory impairment

LY395756, an mGluR2 agonist and mGluR3 antagonist, enhances NMDA receptor expression and function in the normal adult rat prefrontal cortex, but fails to improve working memory and reverse MK801-induced working memory impairment

Augmenting saturated LTP by broadly spaced episodes of theta-burst stimulation in hippocampal area CA1 of adult rats and mice

Dendritic transport element of human arc mRNA confers RNA degradation activity in a translation‐dependent manner

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