Genetic and Pharmacological Evidence for a Novel, Intermediate Phase of Long-Term Potentiation Suppressed by Calcineurin

Winder, Danny G.; Mansuy, Isabelle M.; Osman, Maher M.; Moallem, Theodore M.; Kandel, Eric R.

doi:10.1016/s0092-8674(00)80896-x

Cited by 329 publications

(257 citation statements)

References 42 publications

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…PP2B/calcineurin has been reported to be important for mechanisms of synaptic plasticity such as long-term depression (LTD) (Mulkey et al, 1993;O'Dell and Kandel, 1994) and depotentiation (Zhuo et al, 1999). Furthermore, PP2B/ calcineurin has been shown to alter long-term potentiation (LTP) (Malleret et al, 2001;Winder et al, 1998;Mansuy et al, 1998). Thus, understanding mechanisms of PP2B/ calcineurin regulation could provide valuable insight into regulation of glutamatergic signal transduction.…”

Section: Discussionmentioning

confidence: 99%

NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin

Alagarsamy¹,

Saugstad²,

Warren

et al. 2005

Neuropharmacology

View full text Add to dashboard Cite

Previous reports have shown that activation of N-methyl-D-aspartate (NMDA) receptors potentiates responses to activation of the group I metabotropic glutamate receptor mGluR5 by reversing PKC-mediated desensitization of this receptor. NMDA-induced reversal of mGluR5 desensitization is dependent on activation of protein phosphatases. However, the specific protein phosphatase involved and the precise mechanism by which NMDA receptor activation reduces mGluR desensitization are not known. We have performed a series of molecular, biochemical, and genetic studies to show that NMDA-induced regulation of mGluR5 is dependent on activation of calcium-dependent protein phosphatase 2B/calcineurin (PP2B/CaN). Furthermore, we report that purified calcineurin directly dephosphorylates the C-terminal tail of mGluR5 at sites that are phosphorylated by PKC. Finally, immunoprecipitation and GST fusion protein pull-down experiments reveal that calcineurin interacts with mGluR5, suggesting that these proteins could be colocalized in a signaling complex. Taken together with previous studies, these data suggest that activation of NMDA receptors leads to activation of calcineurin and that calcineurin modulates mGluR5 function by directly dephosphorylating mGluR5 at PKC sites that are involved in desensitization of this receptor.

show abstract

Section: Discussionmentioning

confidence: 99%

NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin

Alagarsamy¹,

Saugstad²,

Warren

et al. 2005

Neuropharmacology

View full text Add to dashboard Cite

show abstract

“…Moreover, pharmacological disruption of memory retention in Drosophila (Xia et al 1998), chicks (Gibbs and Ng 1977;Rosenzweig et al 1993), and rats (Frieder andAllweis 1978, 1982) have all generated strong evidence for distinct intermediate phases of memory. In a similar vein, different forms of neuronal plasticity thought to underlie memory can also be separated into multiple phases by either their time course, mechanism, or both (Montarolo et al 1986;Frey et al 1988;Nguyen et al 1994;Ghirardi et al 1995;Mauelshagen et al 1996;Crow et al 1997;Winder et al 1998;Crow et al 1999;Sutton and Carew 2000).…”

Section: Multiphasic Organization Of Memory Processingmentioning

confidence: 99%

Interaction between Amount and Pattern of Training in the Induction of Intermediate- and Long-Term Memory for Sensitization in Aplysia

Sutton¹,

Ide²,

Masters³

et al. 2002

Learn. Mem.

116

118

View full text Add to dashboard Cite

In Aplysia, three distinct phases of memory for sensitization can be dissociated based on their temporal and molecular features. A single training trial induces short-term memory (STM, lasting <30 min), whereas five trials delivered at 15-min intervals induces both intermediate-term memory (ITM, lasting >90 min) and long-term memory (LTM, lasting >24 h). Here, we explore the interaction of amount and pattern of training in establishing ITM and LTM by examining memory for sensitization after different numbers of trials (each trial = one tail shock) and different patterns of training (massed vs. spaced). Under spaced training patterns, two trials produced STM exclusively, whereas four or five trials each produced both ITM and LTM. Three spaced trials failed to induce LTM but did produce an early decaying form of ITM (E-ITM) that was significantly shorter and weaker in magnitude than the late-decaying ITM (L-ITM) observed after four to five trials. In addition, E-ITM was induced after three trials with both massed and spaced patterns of training. However, L-ITM and LTM after four to five trials require spaced training: Four or five massed trials failed to induce LTM and produced only E-ITM. Collectively, our results indicate that in addition to three identified phases of memory for sensitization-STM, ITM, and LTM-a unique temporal profile of memory, E-ITM, is revealed by varying either the amount or pattern of training.

show abstract

“…The induction of LTP by some patterns of synaptic stimulation, including 5-Hz stimulation, requires activation of Ca 2+ /calmodulin-dependent forms of adenylyl cyclase and a subsequent PKA-mediated suppression of PP1 (Blitzer et al 1995(Blitzer et al , 1998Thomas et al 1996;Winder et al 1998). Changes in Ca 2+ signaling that occur as a result of LTP induction (e.g., because of calmodulin trapping by autophosphorylated ␣CaMKII) might thus hinder activation of Ca 2+ /calmodulin-dependent forms of adenylyl cyclase during 5-Hz stimulation of potentiated synapses, resulting in insufficient levels of PKA activation to inhibit the activity of protein phosphatases that oppose the induction of additional LTP.…”

Section: ␤Ar Activation and Metaplasticitymentioning

confidence: 99%

A Nitric Oxide-Independent and β-Adrenergic Receptor-Sensitive Form of Metaplasticity Limits θ-Frequency Stimulation-Induced LTP in the Hippocampal CA1 Region

Moody¹,

Carlisle²,

O’Dell³

1999

Learn. Mem.

View full text Add to dashboard Cite

The induction of long-term potentiation (LTP) and long-term depression (LTD) at excitatory synapses in the hippocampus can be strongly modulated by patterns of synaptic stimulation that otherwise have no direct effect on synaptic strength. Likewise, patterns of synaptic stimulation that induce LTP or LTD not only modify synaptic strength but can also induce lasting changes that regulate how synapses will respond to subsequent trains of stimulation. Collectively known as metaplasticity, these activity-dependent processes that regulate LTP and LTD induction allow the recent history of synaptic activity to influence the induction of activity-dependent changes in synaptic strength and may thus have an important role in information storage during memory formation. To explore the cellular and molecular mechanisms underlying metaplasticity, we investigated the role of metaplasticity in the induction of LTP by -frequency (5-Hz) synaptic stimulation in the hippocampal CA1 region. Our results show that brief trains of -frequency stimulation not only induce LTP but also activate a process that inhibits the induction of additional LTP at potentiated synapses. Unlike other forms of metaplasticity, the inhibition of LTP induction at potentiated synapses does not appear to arise from activity-dependent changes in NMDA receptor function, does not require nitric oxide signaling, and is strongly modulated by ␤-adrenergic receptor activation. Together with previous findings, our results indicate that mechanistically distinct forms of metaplasticity regulate LTP induction and suggest that one way modulatory transmitters may act to regulate synaptic plasticity is by modulating metaplasticity.

show abstract

Genetic and Pharmacological Evidence for a Novel, Intermediate Phase of Long-Term Potentiation Suppressed by Calcineurin

Cited by 329 publications

References 42 publications

NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin

NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin

Interaction between Amount and Pattern of Training in the Induction of Intermediate- and Long-Term Memory for Sensitization in Aplysia

A Nitric Oxide-Independent and β-Adrenergic Receptor-Sensitive Form of Metaplasticity Limits θ-Frequency Stimulation-Induced LTP in the Hippocampal CA1 Region

Contact Info

Product

Resources

About