A Role for Superoxide in Protein Kinase C Activation and Induction of Long-term Potentiation

Klann, Eric; Roberson, Erik D.; Knapp, Lauren T.; Sweatt, J. David

doi:10.1074/jbc.273.8.4516

Cited by 199 publications

(167 citation statements)

References 54 publications

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“…Shortly after washout of Chel, EPSPs gradually increased and reached a plateau similar to that in control neurons (Fig. 5A), consistent with the long-lasting elevation in PKC activity after LTP induction (37). In control neurons, after the full expression of LTP perisynaptic AMPARs are absent at spine surface, and LFS does not affect LTP (10).…”

Section: Synaptic Translocation Of Perisynaptic Ampars Stabilizes Botsupporting

confidence: 58%

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: Synaptic Translocation Of Perisynaptic Ampars Stabilizes Botsupporting

confidence: 58%

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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“…This is notable because persistent activation of PKC has been shown to be associated with and necessary for the expression of LTP (Klann et al, 1991(Klann et al, , 1993Wang and Feng, 1992;Sacktor et al, 1993;Hrabetova and Sacktor, 1996).…”

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confidence: 99%

Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C

Knapp¹,

2002

Self Cite

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Recent evidence suggests that reactive oxygen species (ROS), including superoxide, are not only neurotoxic but function as small messenger molecules in normal neuronal processes such as synaptic plasticity. Consistent with this idea, we show that brief incubation of hippocampal slices with the superoxidegenerating system xanthine/xanthine oxidase (X/XO) produces a long-lasting potentiation of synaptic transmission in area CA1. We found that X/XO-induced potentiation was associated with a persistent superoxide-dependent increase in autonomous PKC activity that could be isolated via DEAE column chromatography. The X/XO-induced potentiation was blocked by the inhibition of PKC, indicating that the superoxidedependent increase in autonomous PKC activity was necessary for the potentiation. We also found that X/XO-induced potentiation and long-term potentiation (LTP) occluded one another, suggesting that these forms of plasticity share similar cellular mechanisms. In further support of this idea, we found that a persistent, superoxide-dependent increase in autonomous PKC activity isolated via DEAE column chromatography also was associated with LTP. Taken together, our findings indicate that X/XO-induced potentiation and LTP share similar cellular mechanisms, including superoxide-dependent increases in autonomous PKC activity. Finally, our findings suggest that superoxide, in addition to its well known role as a neurotoxin, also can be considered a small messenger molecule critical for normal neuronal signaling.

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“…Interestingly, previous studies suggested that reactive oxygen species can modulate PKC in vitro [52]. The activation of PKC, which phosphorylates NMDA and AMPA receptors [53][54][55], represents one of the principal biochemical pathways necessary to induce Long Term Potentiation (LTP).…”

Section: Fig 1 Representative Confocal Images Of Sod1 Immunofluorescmentioning

confidence: 99%

A new perspective on the role of CuZn superoxide dismutase (SOD1)

et al. 2007

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Abstract:The CuZn superoxide dismutase (SOD1), a member of a group of isoenzymes involved in the scavenger of superoxide anions, is a dimeric carbohydrate free protein, mainly localized in the cytosol. The reactive oxygen species (ROS) are involved in many pathophysiological events correlated with mutagenesis, cancer, degenerative processes and aging. In the first part of this mini-review the well known role of SOD1 and ROS are briefly summarized. Following, a potential novel biological action that SOD1 could exert is described, based on the recent researches demonstrating the secretion of this enzyme in many cellular lines. Moreover, the role of impaired mutant SOD1 secretion, associated with cytoplasmic toxic inclusion, which occurs in familial amyotrophic lateral sclerosis (ALS), is summarized. In addition, a depolarization-dependent release of SOD1 in pituitary GH3 cells and in rat synaptosomes through a calcium and SNARE-dependent mechanism is reported.

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A Role for Superoxide in Protein Kinase C Activation and Induction of Long-term Potentiation

Cited by 199 publications

References 54 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

Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C

A new perspective on the role of CuZn superoxide dismutase (SOD1)

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