Recruitment of Calcium-Permeable AMPA Receptors during Synaptic Potentiation Is Regulated by CaM-Kinase I

Guire, Eric S.; Oh, Michael C.; Soderling, Thomas R.; Derkach, V. A.

doi:10.1523/jneurosci.0384-08.2008

Cited by 142 publications

(168 citation statements)

References 75 publications

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“…Supporting this notion, theta burst stimulation led to the transient synaptic appearance of GluR2-lacking AMPARs (16) and required postsynaptic SNARE-dependent exocytosis (6,10); but high-frequency, stimulation-induced LTP is mediated by synaptic addition of GluR2/3-containing AMPARs (43) and not GluR2-lacking AMPARs (ref. 16, but see ref. 15), and does not require exocytosis (43).…”

Section: Discussionmentioning

confidence: 99%

Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications

Yang

Wang

Zhou

2010

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

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How persistent synaptic and spine modification is achieved is essential to our understanding of developmental refinement of neural circuitry and formation of memory. Within a short period after their induction, both types of modifications can either be stabilized or reversed, but how this reversibility is controlled is largely unknown. We have shown previously that AMPA receptors (AMPARs) are delivered to perisynaptic regions after the induction of long-term potentiation (LTP) but are absent from perisynaptic regions after the full expression of LTP. Here, we report that perisynaptic AMPARs are GluR2-lacking and they translocate to synapses in a protein kinase C (PKC)-dependent manner. Once entering synapses, these AMPARs quickly switch to GluR2-containing in an activity-dependent manner. Absence of postinduction activity or blocking interactions between GluR2 and NSF, or GluR2 and GRIP/ PICK1 results in LTP mediated by GluR2-lacking AMPARs. However, these synaptic GluR2-lacking AMPARs are not sufficient to allow reversibility of LTP. On the other hand, postsynaptic inhibition of PKC activity holds AMPARs at perisynaptic regions. As long as perisynaptic AMPARs are present, both LTP and spine expansion remain labile: they can be reverted to the baseline state together with removal of perisynaptic AMPARs, or they can enter a stabilized state of persistent increase together with synaptic incorporation of perisynaptic AMPARs. Thus, perisynaptic GluR2-lacking AMPARs play a critical role in controlling the reversibility of both synaptic and spine modifications.dendritic spine | long-term potentiation | two-photon imaging P ersistent functional and structural changes in synaptic connections are generally believed to underlie long-lasting modifications in neuronal networks, such as developmental refinement of neural circuitry and memory formation in the adult (1-3). One widely studied form of such long-lasting changes is long-term potentiation (LTP), which is accompanied by long-lasting expansion of dendritic spines (2-4). Within a short time window after LTP induction, both types of modifications can be reversed (5, 6). What controls the labile period of these modifications is of great importance to our understanding of the consolidation of synaptic and spine modifications.Modification of existing synaptic AMPA receptors (AMPARs) and/or addition of new AMPARs to synapses appear to underlie the expression of LTP. Evidence supports a model that newly added AMPARs first appear at extrasynaptic/perisynaptic regions and are subsequently incorporated into synapses (7-11). These perisynaptic AMPARs can be removed by moderate synaptic activity (10) and this removal prevents the full expression of LTP and reverses spine expansion (6, 10). It has been suggested that perisynaptic AMPARs could play a critical role in regulating the persistence of LTP and spine expansion (10,12). This notion is consistent with the observation that stabilization of spine expansion requires synaptic incorporation of new AMPARs (6, 13). A few studies ...

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Section: Discussionmentioning

confidence: 99%

Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications

Yang

Wang

Zhou

2010

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

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“…Interestingly, stimulation of hippocampal neurons with BDNF also increased the synaptic accumulation of GluA1 AMPA receptor subunit, by a mechanism dependent on mTOR and Ca 2þ -and calmodulin-dependent protein kinase kinase (CaMKK) (Caldeira et al, 2007a;Fortin et al, 2012;Guire et al, 2008). BDNF also upregulated GluA1 protein levels in rat forebrain synaptoneurosomes, further indicating that the neurotrophin induces local translation of AMPA receptors at the synapse (Schratt et al, 2004).…”

Section: Bdnf-induced Changes In the Neuronal Proteomementioning

confidence: 95%

“…In addition to the proteins identified in the proteomics analysis discussed above, target oriented studies have shown effects of BDNF in total expression of AMPA and NMDA receptor subunits in cultured hippocampal and cortical neurons (Caldeira et al, 2007a(Caldeira et al, , 2007bFortin et al, 2012;Guire et al, 2008;Narisawa-Saito et al, 1999;Small et al, 1998). Interestingly, stimulation of hippocampal neurons with BDNF also increased the synaptic accumulation of GluA1 AMPA receptor subunit, by a mechanism dependent on mTOR and Ca 2þ -and calmodulin-dependent protein kinase kinase (CaMKK) (Caldeira et al, 2007a;Fortin et al, 2012;Guire et al, 2008).…”

Section: Bdnf-induced Changes In the Neuronal Proteomementioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

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a b s t r a c tBrain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and longterm potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-g (PLC-g) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre-and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short-and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation.This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

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“…Infusion of active CaMKI potentiates AMPARs in cultured neurons through synaptic incorporation of CP-AMPARs, in a manner that requires actin polymerisation. Furthermore, in slices, CA3-CA1 LTP induced by theta burst stimulation recruited CP-AMPARs, and this was prevented by inhibition of CaMKK, an upstream activator of CamKI 141 . However, as yet, the targets of CamKI that mediate synaptic expression of CP-AMPARs have not been identified.…”

Section: Ampar Phosphorylationmentioning

confidence: 98%

“…Together, these data highlight the critical importance of GluA1-S845 phosphorylation in controlling the availability of synaptic CP-AMPARs. Intriguingly, although it does not directly phosphorylate AMPAR subunits, CaMKI has also been implicated in CP-AMPAR expression during hippocampal LTP 141 . Infusion of active CaMKI potentiates AMPARs in cultured neurons through synaptic incorporation of CP-AMPARs, in a manner that requires actin polymerisation.…”

Section: Ampar Phosphorylationmentioning

confidence: 99%

Synaptic AMPA receptor composition in development, plasticity and disease

2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. PrefaceAMPARs are assemblies of four core subunits, GluA1-4, that mediate most fast excitatory neurotransmission. The component subunits determine the functional properties of AMPARs and the prevailing view is that the subunit composition also determines AMPAR trafficking, which is dynamically regulated during development, synaptic plasticity, and in response to neuronal stress in disease. Recently, the subunit-dependence of AMPAR trafficking has been questioned leading to a reappraisal of the field. Here we review what is known, uncertain, conjectured and unknown about the roles of individual subunits and how they impact on AMPAR assembly, trafficking and function under normal and pathological conditions. IntroductionAMPA receptors (AMPARs) are a subtype of ionotropic glutamate receptors that are the 'work-horses' of fast excitatory neurotransmission in the CNS. Developmentallyand activity-regulated changes in the numbers and properties of AMPARs localized at the postsynaptic membrane are essential for excitatory synapse formation, stabilization, synaptic plasticity and neural circuit formation. Consequently, the logistics of the delivery, retention and removal of individual AMPARs with defined subunit compositions at specific synapses is highly complex. A typical cortical or hippocampal pyramidal neuron contains on the order of 10,000 synapses and the AMPARs at each synapse are independently and dynamically regulated in response to developmental cues, synaptic activity and environmental stresses. Furthermore, defects in the processes that control AMPAR assembly, trafficking and synaptic expression are intimately linked to psychiatric and neurological conditions, and also with cognitive decline in neurodegenerative diseases. Remarkable progress has been achieved in understanding how AMPAR trafficking, is orchestrated by a large array of AMPAR interacting proteins. These studies have established a set of hierarchical subunit-specific rules that control AMPAR trafficking under basal and activity-dependent conditions. Furthermore, there has been a growing appreciation that subunit composition can tune the properties of AMPARs to specific conditions. Nonetheless, how AMPARs comprising different subunits are differentially trafficked to control synaptic development, stabilisation and plasticity is a key unanswered question. Here, we provide an overview of the current state of knowledge of subunit-specific AMPAR trafficking and outline what we believe to be the key unresolved questions in the field. 2 Subunit-specific traffickingMost AMPARs are heterotetrameric assemblies of combinations of the subunits GluA1, GluA2, GluA3 and GluA4. AMPARs are expressed in both neurons and glia throughout the CNS 1 and have a turnover time of between 10 hours and 2 days depending on the type of neuron and developmental stage 2,3 . Each subunit has an identical membrane topology and c...

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Recruitment of Calcium-Permeable AMPA Receptors during Synaptic Potentiation Is Regulated by CaM-Kinase I

Cited by 142 publications

References 75 publications

Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications

Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications

BDNF-induced local protein synthesis and synaptic plasticity

Synaptic AMPA receptor composition in development, plasticity and disease

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