Synaptic Plasticity and Translation Initiation

Klann, Eric; Antion, Marcia D.; Banko, Jessica L.; Hou, Lingfei

doi:10.1101/lm.79004

Cited by 101 publications

(92 citation statements)

References 92 publications

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“…Interestingly, our b-AR-dependent metaplasticity did not require activation of mTOR, as it was not blocked by rapamycin. This suggests that capindependent translation, involving internal ribosomal entry sites (IRES) (reviewed by Klann et al 2004), may be recruited by activation of b-ARs 1 h prior to LTP induction. Some dendritic mRNAs that are known to contain IRESs and that may be translated in a cap-independent manner include Arc (activity-regulated cytoskeletal protein), CaMK2-a, and MAP2 (microtubule associated protein-2) (Pinkstaff et al 2001).…”

Section: Discussionmentioning

confidence: 99%

‘Silent’ priming of translation-dependent LTP by β-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors

Tenorio¹,

Connor²,

Guévremont³

et al. 2010

Learn. Mem.

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The capacity for long-term changes in synaptic efficacy can be altered by prior synaptic activity, a process known as "metaplasticity." Activation of receptors for modulatory neurotransmitters can trigger downstream signaling cascades that persist beyond initial receptor activation and may thus have metaplastic effects. Because activation of b-adrenergic receptors (b-ARs) strongly enhances the induction of long-term potentiation (LTP) in the hippocampal CA1 region, we examined whether activation of these receptors also had metaplastic effects on LTP induction. Our results show that activation of b-ARs induces a protein synthesis-dependent form of metaplasticity that primes the future induction of late-phase LTP by a subthreshold stimulus. b-AR activation also induced a long-lasting increase in phosphorylation of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 subunits at a protein kinase A (PKA) site (S845) and transiently activated extracellular signal-regulated kinase (ERK). Consistent with this, inhibitors of PKA and ERK blocked the metaplastic effects of b-AR activation. b-AR activation also induced a prolonged, translation-dependent increase in cell surface levels of GluA1 subunit-containing AMPA receptors. Our results indicate that bARs can modulate hippocampal synaptic plasticity by priming synapses for the future induction of late-phase LTP through up-regulation of translational processes, one consequence of which is the trafficking of AMPARs to the cell surface.

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Section: Discussionmentioning

confidence: 99%

‘Silent’ priming of translation-dependent LTP by β-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors

Tenorio¹,

Connor²,

Guévremont³

et al. 2010

Learn. Mem.

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“…By analogy to growth control in other types of cells, it is highly likely that mTOR acts mainly through its regulation of translational control (Hay and Sonenberg, 2004;Klann et al, 2004) to mediate its effects on dendrite formation and soma size. The translational initiation by mTOR is primarily through two downstream effectors: p70S6Ks and 4EBPs.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Dendritic Morphogenesis by Ras–PI3K–Akt–mTOR and Ras–MAPK Signaling Pathways

Kumar¹,

Zhang²,

Swank³

et al. 2005

J. Neurosci.

532

450

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Dendritic arborization and spine formation are critical for the functioning of neurons. Although many proteins have been identified recently as regulators of dendritic morphogenesis, the intracellular signaling pathways that control these processes are not well understood. Here we report that the Ras-phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway plays pivotal roles in the regulation of many aspects of dendrite formation. Whereas the PI3K-Akt-mTOR pathway alone controlled soma and dendrite size, a coordinated activation together with the Ras-mitogen-activated protein kinase signaling pathway was required for increasing dendritic complexity. Chronic inhibition of PI3K or mTOR reduced soma and dendrite size and dendritic complexity, as well as density of dendritic filopodia and spines, whereas a short-term inhibition promoted the formation of mushroom-shaped spines on cells expressing constitutively active mutants of Ras, PI3K, or Akt, or treated with the upstream activator BDNF. Together, our data underscore the central role of a spatiotemporally regulated key cell survival and growth pathway on trophic regulation of the coordinated development of dendrite size and shape.

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“…The synthesis of proteins has been implicated in many forms of synaptic plasticity and memory formation (for review, see Klann et al 2004;Richter and Sonenberg 2005;Costa-Mattioli et al 2009). Persistent LTP requires translation (Stanton and Sarvey 1984;Frey et al 1988;Kandel 2001;Scharf et al 2002;Gelinas and Nguyen 2005).…”

Section: Discussionmentioning

confidence: 99%

Conversion of short-term potentiation to long-term potentiation in mouse CA1 by coactivation of β-adrenergic and muscarinic receptors

et al. 2012

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Encoding new information requires dynamic changes in synaptic strength. The brain can boost synaptic plasticity through the secretion of neuromodulatory substances, including acetylcholine and noradrenaline. Considerable effort has focused on elucidating how neuromodulatory substances alter synaptic properties. However, determination of the potential synergistic interactions between different neuromodulatory systems remains incomplete. Previous results indicate that coactivation of badrenergic and cholinergic receptors facilitated the conversion of STP to LTP through an extracellular signal-regulated kinase (ERK)-dependent mechanism. ERK signaling has been linked to synaptically localized translation regulation. Thus, we hypothesized that costimulation of noradrenergic and cholinergic receptors could initiate the transformation of STP to LTP through up-regulation of protein synthesis. Our results indicate that a protocol which yields STP (5 Hz, 5 sec) when paired with coapplication of the b-adrenergic agonist, isoproterenol (ISO), and the cholinergic agonist, carbachol (CCh), induces translationdependent LTP in mouse CA1. This form of LTP requires both b1-adrenergic and M1 muscarinic receptor activation, as blocking either receptor subtype prevented LTP induction. Blocking ERK, mTOR, or translation reduced the expression of LTP induced with ISO + CCh. Taken together, our data demonstrate that coactivation of b-adrenergic and muscarinic receptors facilitates the conversion of STP to LTP through a mechanism requiring translation initiation.Memory formation is believed to rely on an activity-dependent, enduring modification of synaptic strength known as long-term potentiation (LTP) (Bliss and Lomo 1973;Bliss and Collingridge 1993;Kandel 2001). LTP has been demonstrated in the hippocampus following events which induce behavioral changes indicative of learning and memory (Whitlock et al. 2006). The hippocampus plays a time-limited role in the establishment of new memories (Scoville and Milner 1957;Zola-Morgan et al. 1986;Neves et al. 2008), a process subject to modification through the release of neuromodulatory transmitters.Cholinergic and noradrenergic neuromodulatory systems can enhance synaptic plasticity (Hu et al. 2007;Dringenberg et al. 2008;Fernández de Sevilla et al. 2008) and long-term memory formation (Cahill et al. 1994 Although the individual contributions of b-and muscarinic receptors to synaptic function have been investigated, the effects of simultaneous activation of these receptors have yet to be fully elucidated. Previous research has demonstrated that coactivation of a-adrenergic and muscarinic receptors facilitates the induction of long-term depression (LTD) (Scheiderer et al. 2008). LTD induced by a-adrenergic and M1 receptors is facilitated through a synergistic elevation of extracellular signal-regulated kinase (ERK) phosphorylation. A similar effect on ERK stimulation was observed when the b-adrenergic receptor agonist, isoproterenol (ISO), was paired with carbachol (CCh), a broad-spectrum mu...

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Synaptic Plasticity and Translation Initiation

Cited by 101 publications

References 92 publications

‘Silent’ priming of translation-dependent LTP by β-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors

‘Silent’ priming of translation-dependent LTP by β-adrenergic receptors involves phosphorylation and recruitment of AMPA receptors

Regulation of Dendritic Morphogenesis by Ras–PI3K–Akt–mTOR and Ras–MAPK Signaling Pathways

Conversion of short-term potentiation to long-term potentiation in mouse CA1 by coactivation of β-adrenergic and muscarinic receptors

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