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The Role of CaMKII Autophosphorylation for NMDA Receptor-Dependent Synaptic Potentiation

Research output: Contribution to journalReview articlepeer-review

Original languageEnglish
JournalNeuropharmacology
Accepted/In press14 May 2021

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  • Giese-review_revised

    Giese_review_revised.docx, 60.8 KB, application/vnd.openxmlformats-officedocument.wordprocessingml.document

    Uploaded date:14 May 2021

    Version:Accepted author manuscript

  • Figure 1

    Figure_1.pdf, 56.6 KB, application/pdf

    Uploaded date:14 May 2021

    Version:Accepted author manuscript

King's Authors

Abstract

Potentiation of glutamatergic synaptic transmission is thought to underlie memory. The induction of this synaptic potentiation relies on activation of NMDA receptors which allows for calcium influx into the post-synapse. A key mechanistic question for the understanding of synaptic potentiation is what signaling is activated by the calcium influx. Here, I review evidences that at mature synapses the elevated calcium levels activate primarily calcium/calmodulin-dependent kinase II (CaMKII) and cause its autophophorylation. CaMKII autophosphorylation leads to calcium-independent activity of the kinase, so that kinase signaling can outlast NMDA receptor-dependent calcium influx. Prolonged CaMKII signaling induces downstream signaling for AMPA receptor trafficking into the post-synaptic density and causes structural enlargement of the synapse. Interestingly, however, CaMKII autophosphorylation does not have such an essential role in NMDA receptor-dependent synaptic potentiation in early postnatal development and in adult dentate gyrus, where neurogenesis occurs. Additionally, in old age memory-relevant NMDA receptor-dependent synaptic plasticity appears to be due to generation of multi-innervated dendritic spines, which does not require CaMKII autophosphorylation. In conclusion, CaMKII autophosphorylation has a conditional role in the induction of NMDA receptor-dependent synaptic potentiation.

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