Limits...
pT305-CaMKII stabilizes a learning-induced increase in AMPA receptors for ongoing memory consolidation after classical conditioning.

Naskar S, Wan H, Kemenes G - Nat Commun (2014)

Bottom Line: CaMKIINtide treatment significantly reduces the learning-induced elevation of both pT305-CaMKII and GluA1 levels and impairs associative long-term memory.Inhibition of proteasomal activity offsets the deleterious effects of CaMKIINtide on both GluA1 levels and long-term memory.These findings suggest that increased levels of pT305-CaMKII play a role in AMPAR-dependent memory consolidation by reducing proteasomal degradation of GluA1 receptor subunits.

View Article: PubMed Central - PubMed

Affiliation: 1] Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK [2].

ABSTRACT
The role of CaMKII in learning-induced activation and trafficking of AMPA receptors (AMPARs) is well established. However, the link between the phosphorylation state of CaMKII and the agonist-triggered proteasomal degradation of AMPARs during memory consolidation remains unknown. Here we describe a novel CaMKII-dependent mechanism by which a learning-induced increase in AMPAR levels is stabilized for consolidation of associative long-term memory. Six hours after classical conditioning the levels of both autophosphorylated pT305-CaMKII and GluA1 type AMPAR subunits are significantly elevated in the ganglia containing the learning circuits of the snail Lymnaea stagnalis. CaMKIINtide treatment significantly reduces the learning-induced elevation of both pT305-CaMKII and GluA1 levels and impairs associative long-term memory. Inhibition of proteasomal activity offsets the deleterious effects of CaMKIINtide on both GluA1 levels and long-term memory. These findings suggest that increased levels of pT305-CaMKII play a role in AMPAR-dependent memory consolidation by reducing proteasomal degradation of GluA1 receptor subunits.

Show MeSH

Related in: MedlinePlus

Effects of training on T305 and T286 phosphorylation of CaMKII during memory consolidationSamples (each containing homogenates of 12 pairs of buccal and cerebral ganglia plus the cerebrobuccal connectives) from three groups of animals, Paired, Unpaired, and Naïve, were used in each replicate experiment. Examples of immunoblot bands shown above the graphs. Full-length blots are shown in Supplementary Fig. 7c and b. The means (±SEM) of pT305-CaMKII (a) or pT286-CaMKII (b) over CaMKII levels are shown (relative integrated density). The values thus calculated for paired samples (a, N=13; b, N=11) and unpaired samples (a, N=13; b, N=11) were normalized to the mean of the values obtained from naïve samples (a, N=13; b, N=11), providing a baseline value of 1 (dashed lines). Both paired and unpaired training similarly increases the level of pT305-CaMKII 6 h after training (a, One-sample t tests: Paired versus baseline, P<0.02; Unpaired versus baseline, P<0.004. Asterisks indicate significant differences compared to the baseline. Two-sample t-test: Paired versus Unpaired group, P=0.09). Unlike T305 phosphorylation, T286 phosphorylation remains unaffected by paired training (b, One-sample t test: Paired versus baseline, P=0.56) and is significantly reduced by unpaired training (b, One-sample t-test: Unpaired versus baseline, P<0.04). These experiment were replicated twice.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4048835&req=5

Figure 6: Effects of training on T305 and T286 phosphorylation of CaMKII during memory consolidationSamples (each containing homogenates of 12 pairs of buccal and cerebral ganglia plus the cerebrobuccal connectives) from three groups of animals, Paired, Unpaired, and Naïve, were used in each replicate experiment. Examples of immunoblot bands shown above the graphs. Full-length blots are shown in Supplementary Fig. 7c and b. The means (±SEM) of pT305-CaMKII (a) or pT286-CaMKII (b) over CaMKII levels are shown (relative integrated density). The values thus calculated for paired samples (a, N=13; b, N=11) and unpaired samples (a, N=13; b, N=11) were normalized to the mean of the values obtained from naïve samples (a, N=13; b, N=11), providing a baseline value of 1 (dashed lines). Both paired and unpaired training similarly increases the level of pT305-CaMKII 6 h after training (a, One-sample t tests: Paired versus baseline, P<0.02; Unpaired versus baseline, P<0.004. Asterisks indicate significant differences compared to the baseline. Two-sample t-test: Paired versus Unpaired group, P=0.09). Unlike T305 phosphorylation, T286 phosphorylation remains unaffected by paired training (b, One-sample t test: Paired versus baseline, P=0.56) and is significantly reduced by unpaired training (b, One-sample t-test: Unpaired versus baseline, P<0.04). These experiment were replicated twice.

Mentions: We found that similar to GluA1 levels (Fig. 2a), levels of pT305-CaMKII were significantly increased at 6 h post conditioning in samples comprising the buccal and cerebral ganglia and the cerebro-buccal connectives from the paired as well as the unpaired groups of animals compared to the naïve controls (Fig. 6a). However, unlike the samples from the paired training group, the level of pT286-CaMKII was significantly lower than baseline in the samples from the unpaired group (Fig. 6b) that showed no response to the CS (see Figs. 1 and 2b). Taken together, these data suggested that for associative memory at 24 h after training, both an elevated level of pT305-CaMKII and at least a baseline level of pT286-CaMKII are required during the period of ongoing memory consolidation at 6 h post-training.


pT305-CaMKII stabilizes a learning-induced increase in AMPA receptors for ongoing memory consolidation after classical conditioning.

Naskar S, Wan H, Kemenes G - Nat Commun (2014)

Effects of training on T305 and T286 phosphorylation of CaMKII during memory consolidationSamples (each containing homogenates of 12 pairs of buccal and cerebral ganglia plus the cerebrobuccal connectives) from three groups of animals, Paired, Unpaired, and Naïve, were used in each replicate experiment. Examples of immunoblot bands shown above the graphs. Full-length blots are shown in Supplementary Fig. 7c and b. The means (±SEM) of pT305-CaMKII (a) or pT286-CaMKII (b) over CaMKII levels are shown (relative integrated density). The values thus calculated for paired samples (a, N=13; b, N=11) and unpaired samples (a, N=13; b, N=11) were normalized to the mean of the values obtained from naïve samples (a, N=13; b, N=11), providing a baseline value of 1 (dashed lines). Both paired and unpaired training similarly increases the level of pT305-CaMKII 6 h after training (a, One-sample t tests: Paired versus baseline, P<0.02; Unpaired versus baseline, P<0.004. Asterisks indicate significant differences compared to the baseline. Two-sample t-test: Paired versus Unpaired group, P=0.09). Unlike T305 phosphorylation, T286 phosphorylation remains unaffected by paired training (b, One-sample t test: Paired versus baseline, P=0.56) and is significantly reduced by unpaired training (b, One-sample t-test: Unpaired versus baseline, P<0.04). These experiment were replicated twice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4048835&req=5

Figure 6: Effects of training on T305 and T286 phosphorylation of CaMKII during memory consolidationSamples (each containing homogenates of 12 pairs of buccal and cerebral ganglia plus the cerebrobuccal connectives) from three groups of animals, Paired, Unpaired, and Naïve, were used in each replicate experiment. Examples of immunoblot bands shown above the graphs. Full-length blots are shown in Supplementary Fig. 7c and b. The means (±SEM) of pT305-CaMKII (a) or pT286-CaMKII (b) over CaMKII levels are shown (relative integrated density). The values thus calculated for paired samples (a, N=13; b, N=11) and unpaired samples (a, N=13; b, N=11) were normalized to the mean of the values obtained from naïve samples (a, N=13; b, N=11), providing a baseline value of 1 (dashed lines). Both paired and unpaired training similarly increases the level of pT305-CaMKII 6 h after training (a, One-sample t tests: Paired versus baseline, P<0.02; Unpaired versus baseline, P<0.004. Asterisks indicate significant differences compared to the baseline. Two-sample t-test: Paired versus Unpaired group, P=0.09). Unlike T305 phosphorylation, T286 phosphorylation remains unaffected by paired training (b, One-sample t test: Paired versus baseline, P=0.56) and is significantly reduced by unpaired training (b, One-sample t-test: Unpaired versus baseline, P<0.04). These experiment were replicated twice.
Mentions: We found that similar to GluA1 levels (Fig. 2a), levels of pT305-CaMKII were significantly increased at 6 h post conditioning in samples comprising the buccal and cerebral ganglia and the cerebro-buccal connectives from the paired as well as the unpaired groups of animals compared to the naïve controls (Fig. 6a). However, unlike the samples from the paired training group, the level of pT286-CaMKII was significantly lower than baseline in the samples from the unpaired group (Fig. 6b) that showed no response to the CS (see Figs. 1 and 2b). Taken together, these data suggested that for associative memory at 24 h after training, both an elevated level of pT305-CaMKII and at least a baseline level of pT286-CaMKII are required during the period of ongoing memory consolidation at 6 h post-training.

Bottom Line: CaMKIINtide treatment significantly reduces the learning-induced elevation of both pT305-CaMKII and GluA1 levels and impairs associative long-term memory.Inhibition of proteasomal activity offsets the deleterious effects of CaMKIINtide on both GluA1 levels and long-term memory.These findings suggest that increased levels of pT305-CaMKII play a role in AMPAR-dependent memory consolidation by reducing proteasomal degradation of GluA1 receptor subunits.

View Article: PubMed Central - PubMed

Affiliation: 1] Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK [2].

ABSTRACT
The role of CaMKII in learning-induced activation and trafficking of AMPA receptors (AMPARs) is well established. However, the link between the phosphorylation state of CaMKII and the agonist-triggered proteasomal degradation of AMPARs during memory consolidation remains unknown. Here we describe a novel CaMKII-dependent mechanism by which a learning-induced increase in AMPAR levels is stabilized for consolidation of associative long-term memory. Six hours after classical conditioning the levels of both autophosphorylated pT305-CaMKII and GluA1 type AMPAR subunits are significantly elevated in the ganglia containing the learning circuits of the snail Lymnaea stagnalis. CaMKIINtide treatment significantly reduces the learning-induced elevation of both pT305-CaMKII and GluA1 levels and impairs associative long-term memory. Inhibition of proteasomal activity offsets the deleterious effects of CaMKIINtide on both GluA1 levels and long-term memory. These findings suggest that increased levels of pT305-CaMKII play a role in AMPAR-dependent memory consolidation by reducing proteasomal degradation of GluA1 receptor subunits.

Show MeSH
Related in: MedlinePlus