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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.

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Related in: MedlinePlus

GluA1 receptors are present in post-synaptic sites within the ‘learning ganglia’Co-localization of GluA1 (green fluorescence) and PSD-95 (red fluorescence) in the buccal (top set of panels) and cerebral ganglia (bottom set of panels). The positions of neuronal cell bodies were mapped by using DAPI staining of the nuclei. The neuropile is indicated by an asterisk. The large panels on the right show the distribution of co-localized PSD-95 and GluA1 immunopositive pixels (real size of each pixel, 0.25 μm x 0.25 μm), in both the neuronal cell body region and the neuropile. Arrows indicate examples of neuronal cell bodies with particularly strong co-localization of GluA1 with PSD-95, both in the soma and the axon hillock. Scale bars represent 50 μm. This experiment was replicated three times.
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Figure 3: GluA1 receptors are present in post-synaptic sites within the ‘learning ganglia’Co-localization of GluA1 (green fluorescence) and PSD-95 (red fluorescence) in the buccal (top set of panels) and cerebral ganglia (bottom set of panels). The positions of neuronal cell bodies were mapped by using DAPI staining of the nuclei. The neuropile is indicated by an asterisk. The large panels on the right show the distribution of co-localized PSD-95 and GluA1 immunopositive pixels (real size of each pixel, 0.25 μm x 0.25 μm), in both the neuronal cell body region and the neuropile. Arrows indicate examples of neuronal cell bodies with particularly strong co-localization of GluA1 with PSD-95, both in the soma and the axon hillock. Scale bars represent 50 μm. This experiment was replicated three times.

Mentions: GluA1 receptors were detected as immunopositive punctae both in the cell bodies of neurons of the feeding system (known to respond to glutamate and AMPA33) and in the neuropile region where most of the synaptic contacts are made between the neurites of neurons (snail neurons do not possess dendrites) (Fig. 3). A quantitative analysis of the confocal images revealed that the majority (between 60 and 64 %) of the green and red pixels (representing GluA1 and PSD-95 immunoreactivity, respectively) co-localized and showed a high level of intensity correlation in the buccal and cerebral ganglia as well as separately in both the neuropile and on the periphery of neuronal somata in these two ganglia (Supplementary Fig. 2).


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)

GluA1 receptors are present in post-synaptic sites within the ‘learning ganglia’Co-localization of GluA1 (green fluorescence) and PSD-95 (red fluorescence) in the buccal (top set of panels) and cerebral ganglia (bottom set of panels). The positions of neuronal cell bodies were mapped by using DAPI staining of the nuclei. The neuropile is indicated by an asterisk. The large panels on the right show the distribution of co-localized PSD-95 and GluA1 immunopositive pixels (real size of each pixel, 0.25 μm x 0.25 μm), in both the neuronal cell body region and the neuropile. Arrows indicate examples of neuronal cell bodies with particularly strong co-localization of GluA1 with PSD-95, both in the soma and the axon hillock. Scale bars represent 50 μm. This experiment was replicated three times.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: GluA1 receptors are present in post-synaptic sites within the ‘learning ganglia’Co-localization of GluA1 (green fluorescence) and PSD-95 (red fluorescence) in the buccal (top set of panels) and cerebral ganglia (bottom set of panels). The positions of neuronal cell bodies were mapped by using DAPI staining of the nuclei. The neuropile is indicated by an asterisk. The large panels on the right show the distribution of co-localized PSD-95 and GluA1 immunopositive pixels (real size of each pixel, 0.25 μm x 0.25 μm), in both the neuronal cell body region and the neuropile. Arrows indicate examples of neuronal cell bodies with particularly strong co-localization of GluA1 with PSD-95, both in the soma and the axon hillock. Scale bars represent 50 μm. This experiment was replicated three times.
Mentions: GluA1 receptors were detected as immunopositive punctae both in the cell bodies of neurons of the feeding system (known to respond to glutamate and AMPA33) and in the neuropile region where most of the synaptic contacts are made between the neurites of neurons (snail neurons do not possess dendrites) (Fig. 3). A quantitative analysis of the confocal images revealed that the majority (between 60 and 64 %) of the green and red pixels (representing GluA1 and PSD-95 immunoreactivity, respectively) co-localized and showed a high level of intensity correlation in the buccal and cerebral ganglia as well as separately in both the neuropile and on the periphery of neuronal somata in these two ganglia (Supplementary Fig. 2).

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