Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP

Lü, Yuan; Allen, Margaret L.; Halt, Amy R; Weisenhaus, Michael; Dallapiazza, Robert F.; Hall, Duane D.; Usachev, Yuriy M.; McKnight, G. Stanley; Hell, Johannes

doi:10.1038/sj.emboj.7601884

Cited by 158 publications

(281 citation statements)

References 81 publications

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“…Recent studies showed that LTP induces a rapid but transient increase in synaptic expression of GluR2-lacking Ca 2ϩ -permeable AMPARs in 10 to 12-day-old mice. Although these receptors are subsequently replaced by GluR2-containing AMPARs, their transient expression in the synapse increases Ca 2ϩ permeability, and may contribute to the stabilization of LTP (Plant et al, 2006;Lu et al, 2007b). At later developmental stages GluR2-lacking AMPARs are no longer required for the early phase of LTP (Lu et al, 2007b), which may explain the discrepancies found in the literature concerning this issue (Adesnik and Nicoll, 2007;Gray et al, 2007).…”

Section: Role Of Ampars In Ltpcontrasting

confidence: 50%

“…Although these receptors are subsequently replaced by GluR2-containing AMPARs, their transient expression in the synapse increases Ca 2ϩ permeability, and may contribute to the stabilization of LTP (Plant et al, 2006;Lu et al, 2007b). At later developmental stages GluR2-lacking AMPARs are no longer required for the early phase of LTP (Lu et al, 2007b), which may explain the discrepancies found in the literature concerning this issue (Adesnik and Nicoll, 2007;Gray et al, 2007). Under resting conditions AMPARs are recycled in a constitutive manner between synapses and intracellular membrane compartments, where they are sorted for degradation or for reinsertion at synapses (Ehlers, 2000;Passafaro et al, 2001) (see above).…”

Section: Role Of Ampars In Ltpmentioning

confidence: 99%

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Regulation of AMPA receptors and synaptic plasticity

et al. 2009

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Section: Role Of Ampars In Ltpcontrasting

confidence: 50%

Section: Role Of Ampars In Ltpmentioning

confidence: 99%

Regulation of AMPA receptors and synaptic plasticity

et al. 2009

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“…16, but see ref. 15), and does not require exocytosis (43). Further testing is required to determine whether different forms of LTP coexist and, if so, under what conditions one form or the other is selectively induced, and whether the expression is synapse-specific given the known heterogeneity of synaptic compositions (44).…”

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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“…Recent evidence indicates that the molecular composition of synaptic AMPA receptors is altered following activity-dependent changes in synaptic strength ( [31][32][33]; but also note [34,35]). Similarly, alterations in AMPA receptor trafficking are implicated in leptin-induced LTP as an increase in AMPA receptor rectification accompanied the leptin-driven increase in synaptic efficacy.…”

Section: Leptin-induced Long-term Potentiation At Adult Hippocampal Cmentioning

confidence: 99%

Leptin regulation of hippocampal synaptic function in health and disease

Irving

Harvey

2014

Phil. Trans. R. Soc. B

102

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The endocrine hormone leptin plays a key role in regulating food intake and body weight via its actions in the hypothalamus. However, leptin receptors are highly expressed in many extra-hypothalamic brain regions and evidence is growing that leptin influences many central processes including cognition. Indeed, recent studies indicate that leptin is a potential cognitive enhancer as it markedly facilitates the cellular events underlying hippocampal-dependent learning and memory, including effects on glutamate receptor trafficking, neuronal morphology and activity-dependent synaptic plasticity. However, the ability of leptin to regulate hippocampal synaptic function markedly declines with age and aberrant leptin function has been linked to neurodegenerative disorders such as Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive enhancing role for the hormone leptin and discuss the therapeutic potential of using leptin-based agents to treat AD.

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Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP

Cited by 158 publications

References 81 publications

Regulation of AMPA receptors and synaptic plasticity

Regulation of AMPA receptors and synaptic plasticity

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

Leptin regulation of hippocampal synaptic function in health and disease

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