Rapid Erasure of Long-Term Memory Associations in the Cortex by an Inhibitor of PKM

Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
Science (Impact Factor: 33.61). 09/2007; 317(5840):951-3. DOI: 10.1126/science.1144334
Source: PubMed


Little is known about the neuronal mechanisms that subserve long-term memory persistence in the brain. The components of the remodeled synaptic machinery, and how they sustain the new synaptic or cellwide configuration over time, are yet to be elucidated. In the rat cortex, long-term associative memories vanished rapidly after local application of an inhibitor of the protein kinase C isoform, protein kinase M zeta (PKMzeta). The effect was observed for at least several weeks after encoding and may be irreversible. In the neocortex, which is assumed to be the repository of multiple types of long-term memory, persistence of memory is thus dependent on ongoing activity of a protein kinase long after that memory is considered to have consolidated into a long-term stable form.

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    • "Neural Plasticity reported [16] [29]. However, there have been no studies published on immediate-early gene (IEG) expression with respect to LTP and PKMí µí¼-related mechanisms of plasticity in the IC after nerve injury. "
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    ABSTRACT: The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.
    Neural Plasticity 10/2015; 2015(6009):601767. DOI:10.1155/2015/601767 · 3.58 Impact Factor
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    • "In our study, we circumvented the restriction of the cannulation method by exploiting a unique feature of compounds that are able to reverse late-phase LTP. Unlike pharmacological compounds which must be infused either immediately before, during, or immediately after the learning episode (e.g., [20]), compounds like ZIP are able to impair memory even days after the learning episode [3] [21]. The fact that ZIP can be infused even days after the learning episode obviates the need for indwelling guide cannulas. "
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    • "The present results add to the accumulating evidence that PKMζ plays crucial roles in the persistence of long - term memory and long - term synaptic plasticity in both vertebrates and invertebrates ( Drier et al . , 2002 ; Ling et al . , 2002 ; Serrano et al . , 2005 ; Pastalkova et al . , 2006 ; Shema et al . , 2007 ) ."
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