αCaMKII autophosphorylation: a fast track to memory

Irvine, Elaine E.; Hertzen, Laura S J von; Plattner, Florian; Giese, K. Peter

doi:10.1016/j.tins.2006.06.009

Cited by 90 publications

(70 citation statements)

References 58 publications

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“…The autophosphorylation of ␣CaMKII at Thr286 is postulated to play a major role in synaptic plasticity and learning, including spatial learning (Mayford et al, 1996;Giese et al, 1998;Irvine et al, 2005Irvine et al, , 2006. This autophosphorylation is also critical for contextual fear conditioning: training in this task increases autophosphorylation of ␣CaMKII at Thr286 in spines in the lateral amygdala (LA), whereas blockade of activation of CaMKII impairs both synaptic plasticity and fear conditioning in the LA (Rodrigues et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning

Zhou¹,

Takahashi²,

Li³

et al. 2007

J. Neurosci.

160

132

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The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/ calmodulin-dependent protein kinase II (CaMKII). To determine the function of these interactions, we derived transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the estrogen receptor ligand-binding domain LBD G521R . Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBD G521R -cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of ␣CaMKII, lowers phosphorylation of a key CaMKII substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor 1), and produces deficits in hippocampal long-term potentiation and spatial learning. Together our results demonstrate the importance of interactions between CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning.

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Section: Discussionmentioning

confidence: 99%

Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning

Zhou¹,

Takahashi²,

Li³

et al. 2007

J. Neurosci.

160

132

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“…We investigated the role of ␣CaMKII, a key molecular determinant of memory formation (Irvine et al 2006), in extinction of contextual fear and spatial memories by testing how a heterozygous T286A point mutation at the autophosphorylation site of this kinase (␣CaMKII T286A+/-) affects the mechanisms that extinguish memories. Although mice that are homozygous for the ␣CaMKII T286A mutation and deficient in autophosphorylation exhibit impairments in contextual fear conditioning and spatial learning in the water maze (Giese et al 1998;Ohno et al 2002Ohno et al , 2005Ohno et al , 2006Need and Giese 2003;Irvine et al 2005), ␣CaMKII T286A+/-mice were normal in the formation of contextual and spatial memories tested 24 h after training.…”

Section: Discussionmentioning

confidence: 99%

“…␣-Calcium/calmodulin-dependent protein kinase II (␣CaMKII) is an abundant synaptic protein that is central to memory formation (Irvine et al 2006) and long-term potentiation (LTP), an activity-dependent strengthening of synapses that is thought to underlie learning and memory (Lisman et al 2002). A broad range of genetic lesions of ␣CaMKII signaling has been demonstrated to block both learning and LTP (Elgersma et al 2004).…”

mentioning

confidence: 99%

Autophosphorylation of αCaMKII is differentially involved in new learning and unlearning mechanisms of memory extinction

Kimura¹,

Silva²,

Ohno³

2008

Learn. Mem.

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Accumulating evidence indicates the key role of ␣-calcium/calmodulin-dependent protein kinase II (␣CaMKII) in synaptic plasticity and learning, but it remains unclear how this kinase participates in the processing of memory extinction. Here, we investigated the mechanism by which ␣CaMKII may mediate extinction by using heterozygous knock-in mice with a targeted T286A mutation that prevents the autophosphorylation of this kinase (␣CaMKII T286A+/-). Remarkably, partial reduction of ␣CaMKII function due to the T286A +/-mutation prevented the development of extinction without interfering with initial hippocampus-dependent memory formation as assessed by contextual fear conditioning and the Morris water maze. It is hypothesized that the mechanism of extinction may differ depending on the interval at which extinction training is started, being more akin to "new learning" at longer intervals and "unlearning" or "erasure" at shorter intervals. Consistent with this hypothesis, we found that extinction conducted 24 h, but not 15 min, after contextual fear training showed spontaneous recovery (reappearance of extinguished freezing responses) 21 d following the extinction, representing behavioral evidence for new learning and unlearning mechanisms underlying extinction 24 h and 15 min post-training, respectively. Importantly, the ␣CaMKII T286A+/-mutation blocked new learning of contextual fear memory extinction, whereas it did not interfere with unlearning processes. Our results demonstrate a genetic dissociation of new learning and unlearning mechanisms of extinction, and suggest that ␣CaMKII is responsible for extinguishing memories specifically through new learning mechanisms.

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“…1). Accordingly, CaMKII activity is increased during memory formation (e.g., Cammarota et al 1998) and blockade of CaMKII substantially impairs memory formation (for reviews, see Lisman et al 2002;Elgersma et al 2004;Irvine et al 2006;Wayman et al 2008;Lucchesi et al 2011;Coultrap and Bayer 2012). This indicates that CaMKII has an essential function in memory formation.…”

Section: Camkiimentioning

confidence: 99%

The roles of protein kinases in learning and memory

2013

Self Cite

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In the adult mammalian brain, more than 250 protein kinases are expressed, but only a few of these kinases are currently known to enable learning and memory. Based on this information it appears that learning and memory-related kinases either impact on synaptic transmission by altering ion channel properties or ion channel density, or regulate gene expression and protein synthesis causing structural changes at existing synapses as well as synaptogenesis. Here, we review the roles of these kinases in short-term memory formation, memory consolidation, memory storage, retrieval, reconsolidation, and extinction. Specifically, we discuss the roles of calcium/calmodulin-dependent kinase II (CaMKII

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αCaMKII autophosphorylation: a fast track to memory

Cited by 90 publications

References 58 publications

Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning

Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning

Autophosphorylation of αCaMKII is differentially involved in new learning and unlearning mechanisms of memory extinction

The roles of protein kinases in learning and memory

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