Proteases involved in long-term potentiation

Tomimatsu, Yoshiro; Idemoto, Satoru; Moriguchi, Shigeki; Watanabe, Soichi; Nakanishi, Hiroshi

doi:10.1016/s0024-3205(02)02285-3

Cited by 82 publications

(58 citation statements)

References 23 publications

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“…However, this would be expected to interfere with any contributions of the perisynaptic pool to the maintenance of baseline synaptic responses and we saw no evidence of this at control inputs. TBS, in addition to its actions on kinases, causes the breakdown of actin crosslinking proteins in the subsynaptic cytoskeleton; the relevant proteases also cleave transmembrane adhesion receptors that play a critical role in LTP-related actin polymerization (40)(41)(42). Replacing the degraded elements might well require the 45-60 min needed to prepare primed high threshold spines for the arrival of TBS2.…”

Section: Discussionmentioning

confidence: 99%

Synaptic evidence for the efficacy of spaced learning

Kramár¹,

Babayan²,

Gavin

et al. 2012

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

142

189

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The superiority of spaced vs. massed training is a fundamental feature of learning. Here, we describe unanticipated timing rules for the production of long-term potentiation (LTP) in adult rat hippocampal slices that can account for one temporal segment of the spaced trials phenomenon. Successive bouts of naturalistic theta burst stimulation of field CA1 afferents markedly enhanced previously saturated LTP if spaced apart by 1 h or longer, but were without effect when shorter intervals were used. Analyses of Factin-enriched spines to identify potentiated synapses indicated that the added LTP obtained with delayed theta trains involved recruitment of synapses that were "missed" by the first stimulation bout. Single spine glutamate-uncaging experiments confirmed that less than half of the spines in adult hippocampus are primed to undergo plasticity under baseline conditions, suggesting that intrinsic variability among individual synapses imposes a repetitive presentation requirement for maximizing the percentage of potentiated connections. We propose that a combination of local diffusion from initially modified spines coupled with much later membrane insertion events dictate that the repetitions be widely spaced. Thus, the synaptic mechanisms described here provide a neurobiological explanation for one component of a poorly understood, ubiquitous aspect of learning.A n extensive body of experimental work indicates that periodic exposure to the same material results in better retention than a single "cramming" session. Although this distributed practice effect was first recognized in late 19th century (1-3), and has since been the subject of a very large psychological literature (4), the neurobiological processes that give rise to the phenomenon are poorly understood. Activity-dependent synaptic plasticity, and, in particular, long-term potentiation (LTP) of glutamatergic transmission, is thought to underlie rapid storage of new information (5, 6). Therefore, it is surprising that little experimental attention has been given to the possibility that specialized features of LTP may contribute to the spaced trials (distributed practice) effect. This likely reflects the lack of data indicating that the substrates of the potentiation effect include properties that are engaged, or enhanced, only by widely spaced stimulation episodes. Specifically, several types of studies point to the conclusion that the elaborate processes yielding fully developed LTP reach completion within 10-15 min (5, 7, 8); these findings do not include results suggestive of a delayed capacity for triggering additional changes to already potentiated synapses. There is considerable evidence for a later LTP stabilization step involving protein synthesis (9), but the effects of this on subsequent plasticity involve inputs other than those already expressing potentiation (10).Here, we describe a set of mechanisms and timing rules in hippocampus that result in widely spaced episodes of theta burst stimulation (TBS) generating a much greater degree of LT...

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Section: Discussionmentioning

confidence: 99%

Synaptic evidence for the efficacy of spaced learning

Kramár¹,

Babayan²,

Gavin

et al. 2012

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

142

189

View full text Add to dashboard Cite

show abstract

“…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.

201

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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“…Numerous studies have demonstrated that in hippocampus PAR2 and proteases are involved in synaptogenesis, long-term potentiation and depression and may contribute to excitotoxicity through cleavage of the NR1 subunit of NMDA glutamate receptors (Hoffman et al, 1998;Nicole et al, 2001;Qian et al, 1993;Scarisbrick et al, 2001;Tomimatsu et al, 2002;Yepes et al, 2002). PAR2 signalling therefore has a neuromodulatory role.…”

Section: What Is the Function Of Par2 And Proteinases In Brain?mentioning

confidence: 99%

Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson’s Disease

et al. 2015

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In neurologically normal brain expression of proteinase-activated receptor-2, activating proteinases and proteinase inhibitors was found in neurons and microglia and did not specifically associate with regions prone to neurodegeneration in Parkinson's disease. InParkinson's disease brain, alterations in the amount of immunoreactivity for proteinaseactivated receptor-2, trypsin-2 and both serpin proteinase inhibitors were found throughout the brain. In neurons, there was a decrease in neurons positive for proteinase inhibitors with increasing Braak α-synuclein stage in the dorsal motor nucleus, locus coeruleus, substantia nigra and primary motor cortex. In contrast, in the cingulate cortex, proteinase-activated receptor-2 expression had a positive correlation to increase with higher Braak α-synuclein stage rating and serpin-A13 was increased in early Parkinson's disease cases compared to controls. In microglia, increased expression occurred for the serpins (dorsal motor nucleus of vagus and substantia nigra), trypsin-2 (dorsal motor nucleus of vagus and primary motor cortex) and proteinase-activated receptor-2 (locus coeruleus and cingulate cortex) that progressively increased with advancing Parkinson's disease severity.In cingulate cortex, the covariate dyskinesia had a significant effect on the the adjusted means for trypsin-2 labelled neurons and microglia and the covariate psychosis had a significant effect on neurons labelled with serpin-A5. While in primary motor cortex, the covariate dyskinesia had a significant effect on the the adjusted means for neurons labelled with serpin-A5, serpin-A13 and trypsin-2. Analysis of Parkinson's disease cases found that serpin and trypsin-2 expression in midbrain and cerebral cortex was different in cases with dyskinesia and psychosis compared to those with no treatment induced side-effects. This study showed that there was altered expression in brain of proteinase-activated receptor-2 and some proteins that can control its function in Parkinson's disease. Given the role of PAR2 expression in Parkinson's disease 3 proteinase-activated receptor-2 in neuroinflammation, drugs that mitigate these changes could be neuroprotective when administered to patients with Parkinson's disease.

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Proteases involved in long-term potentiation

Cited by 82 publications

References 23 publications

Synaptic evidence for the efficacy of spaced learning

Synaptic evidence for the efficacy of spaced learning

Integrin-driven actin polymerization consolidates long-term potentiation

Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson’s Disease

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