Development of hippocampal long-term potentiation is reduced by recently introduced calpain inhibitors

Cerro, Sonia del; Larson, John; Oliver, Michael W.; Lynch, Gary

doi:10.1016/0006-8993(90)90660-4

Cited by 98 publications

(48 citation statements)

References 24 publications

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“…When this cocktail was used without kinase inhibitor, robust LTP was observed. This finding is of interest because of previous work suggesting that LTP induction could be blocked by bath application of leupeptin (del Cerro et al, 1990;Denny et al, 1990). This led to the proposal that LTP induction required calpain activation in the postsynaptic cell.…”

Section: Discussionmentioning

confidence: 75%

Postsynaptic Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase Type II Block Induction But Not Maintenance of Pairing-Induced Long-Term Potentiation

1997

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The role of postsynaptic kinases in the induction and maintenance of long-term potentiation (LTP) was studied in the CA1 region of the rat hippocampal slice. A peptide inhibitor for the catalytic domain of calcium/calmodulin-dependent protein kinase type II (CaM-kinase) was applied through a perfused patch pipette. The inhibitor completely blocked both the shortterm potentiation and LTP induced by a pairing protocol. This indicates that the kinase or kinases affected by the peptide are downstream from depolarization in the LTP cascade. The ability to block LTP required that measures be taken to interfere with degradation of the peptide kinase inhibitor by endogenous proteases; either addition of protease inhibitors or modifications of the peptide itself greatly enhanced the effectiveness of the peptide. Protease inhibitors by themselves or control peptide did not block LTP induction. To study the effect of kinase inhibitor on LTP maintenance, we induced LTP in one pathway. Subsequent introduction of the kinase inhibitor blocked the induction of LTP in a second pathway, but it did not affect maintenance of LTP in the first. The implications for the role of kinases in LTP maintenance are discussed. Key words: long-term potentiation; calcium/calmodulindependent kinase; peptide inhibitors; hippocampal slices; whole-cell recording; intracellular perfusion; protease inhibitors; fluorescent imagingLong-term potentiation (LTP) in the CA1 region of the hippocampus is the best-studied example of the activity-dependent synaptic modifications that may underlie learning and memory (Bliss and Collingridge, 1993;Malenka and Nicoll, 1993) There is now considerable biochemical, physiological, and genetic evidence for the involvement of protein kinases in LTP induction (Colley and Routtenberg, 1993;Suzuki, 1994;Roberson et al., 1996). Some experiments have shown specifically that blocking different postsynaptic kinases is sufficient to block LTP induction (Malenka et al., 1989;Malinow et al., 1989;O'Dell et al., 1991;Wang and Feng, 1992;Hvalby et al., 1994;Blitzer et al., 1995;Feng, 1995;Wang and Kelly, 1996). Furthermore, introduction of protein kinase C (C -kinase) or calcium /calmodulin-dependent protein kinase type II (C aM-kinase) (Hu et al., 1987; McGladeMcCulloh et al., 1993;L ledo et al., 1995) or their activators (Wang and Kelly, 1995) into the postsynaptic cell results in synaptic potentiation that may occlude tetanus-induced LTP (Wang and Kelly, 1995).Although there is general agreement that postsynaptic kinases are involved in LTP induction, their exact role remains unclear. LTP is initiated by C a 2ϩ entry through the NMDA channels (Bliss and Collingridge, 1993), an entry that requires depolarization (Mayer et al., 1984;Nowak et al., 1984). The depolarization may be provided by dendritic action potentials (Jaffe et al., 1992;Magee and Johnston, 1997) and the EPSP, both of which depend on voltage-dependent channels Sakmann, 1994, 1995;Andreasen and Lambert, 1995), which themselves may be regulated by phosphorylation ...

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Section: Discussionmentioning

confidence: 75%

Postsynaptic Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase Type II Block Induction But Not Maintenance of Pairing-Induced Long-Term Potentiation

1997

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“…However, the model's explanatory power is limited by the lack of any obvious link between the rapid mechanisms described above and the later, protein synthesis-dependent components of consolidation. There is evidence that theta stimulation causes the immediate proteolysis of key structural proteins (40,(43)(44)(45)(46), an event that could both pave the way for a reorganization of the actin network and create a need for newly synthesized proteins. In this regard, it will be of interest to test the nonintuitive prediction that protease inhibitors reported to block LTP will also prevent activity-induced increases in spine F-actin.…”

Section: Discussionmentioning

confidence: 99%

Integrin-driven actin polymerization consolidates long-term potentiation

Kramár¹,

Lin²,

Rex

et al. 2006

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

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204

230

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Long-term potentiation (LTP), like memory, becomes progressively more resistant to disruption with time after its formation. Here we show that threshold conditions for inducing LTP cause a rapid, long-lasting increase in polymerized filamentous actin in dendritic spines of adult hippocampus. Two independent manipulations that reverse LTP disrupted this effect when applied shortly after induction but not 30 min later. Function-blocking antibodies to ␤1 family integrins selectively eliminated both actin polymerization and stabilization of LTP. We propose that the initial stages of consolidation involve integrin-driven events common to cells engaged in activities that require rapid morphological changes.adenosine ͉ consolidation ͉ hippocampus ͉ spines ͉ theta burst

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“…Calpain inhibitors, for instance, block both LTP (Cerro et al, 1990;Denny et al, 1990a;Fitzpatrick et al, 1992) and LTD (Fig. 5).…”

Section: Pkm and The Divergence And Convergence Of Signal Transductiomentioning

confidence: 92%

“…Because calpain, a Ca 2ϩ -dependent protease, may contribute to both the formation and the degradation of PKM (Al and Cohen, 1993), we examined the effect on LTD of the application of calpain inhibitor I, a selective, membrane-permeable inhibitor of the protease that effectively blocks LTP, but not early NMDA-dependent potentiation (Cerro et al, 1990;Denny et al, 1990a;Fitzpatrick et al, 1992). Calpain inhibitor I [6 M in 0.1% dimethyl sulfoxide (DMSO)] blocked the formation of LTD without affecting STD (Fig.…”

Section: An Essential Role For Calpain Proteolysis In Ltd and Pkm Dowmentioning

confidence: 99%

Bidirectional Regulation of Protein Kinase Mζ in the Maintenance of Long-Term Potentiation and Long-Term Depression

1996

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Long-term potentiation (LTP) and long-term depression (LTD) are persistent modifications of synaptic efficacy that may contribute to information storage in the CA1 region of the hippocampus. Persistently enhanced phosphorylation has been implicated in the maintenance phase of LTP. This hypothesis is supported by our previous observation that protein kinase M (PKM), the constitutively active catalytic fragment of a single protein kinase C isoform (PKC), increases in LTP maintenance. In contrast, dephosphorylation may be important in LTD maintenance, because phosphatase inhibitors reverse established LTD, in addition to blocking its induction. Because phosphorylation is determined by a balance of phosphatases and kinases, both increases in phosphatase activity and decreases in kinase activity could contribute to LTD. We now report that the reduction of protein kinase activity by H7, as well as selective inhibition of PKC by chelerythrine, mimics and occludes the maintenance phase of homosynaptic LTD in rat hippocampal slices. Conversely, saturated LTD occludes the synaptic depression caused by chelerythrine. Biochemical analysis demonstrates a decrease of PKM, as well as PKCs ␥ and ⑀, in LTD maintenance and a concomitant loss of constitutive PKC activity. LTD and the downregulation of PKM are prevented by NMDA receptor antagonists and Ca 2ϩ -dependent protease inhibitors. Both LTD and the downregulation of PKM are reversible by high-frequency afferent stimulation. Our findings indicate that the molecular mechanisms of LTP and LTD maintenance are inversely related through the bidirectional regulation of PKC.

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Development of hippocampal long-term potentiation is reduced by recently introduced calpain inhibitors

Cited by 98 publications

References 24 publications

Postsynaptic Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase Type II Block Induction But Not Maintenance of Pairing-Induced Long-Term Potentiation

Postsynaptic Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase Type II Block Induction But Not Maintenance of Pairing-Induced Long-Term Potentiation

Integrin-driven actin polymerization consolidates long-term potentiation

Bidirectional Regulation of Protein Kinase Mζ in the Maintenance of Long-Term Potentiation and Long-Term Depression

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