Selective targeting of mRNA and following protein synthesis of CaMKIIα at the long-term potentiation-induced site

Abstract

Late-phase long-term potentiation (L-LTP) in hippocampus, thought to be the cellular basis of long-term memory, requires new protein synthesis. Neural activity enhances local protein synthesis in dendrites, which in turn mediates long-lasting synaptic plasticity. Ca 2+ /calmodulin-dependent protein kinase IIα (CaMKIIα) is a locally synthesized protein crucial for this plasticity, as L-LTP is impaired when its local synthesis is eliminated. However, the distribution of Camk2a mRNA during L-LTP induction remains unclear. In this study, we investigated the dendritic targeting of Camk2a mRNA after highfrequency stimulation, which induces L-LTP in synapses of perforant path and granule cells in the dentate gyrus in vivo. In situ hybridization studies revealed that Camk2a mRNA was immediately but transiently targeted to the site receiving high-frequency stimulation. This was associated with an increase in de novo protein synthesis of CaMKIIα. These results suggest that dendritic translation of CaMKIIα is locally mediated where L-LTP is induced. This phenomenon may be one of the essential processes for memory establishment.

Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond

“…Additionally, neurons host up to several thousand synapses where mRNA localisation and local translation are key for ensuring the rapid spatio-temporal regulation of protein synthesis required for synaptic plasticity [ 3 , 6 , 72 ]. For instance, Camk2ɑ mRNA was found to localise to dendrites at sites receiving high-frequency stimulation [ 73 ], whereas NMDA-induced neuronal activation was demonstrated to trigger the translocation of Calmodulin-3 mRNA into dendrites in rat cortical neurons [ 74 ]. Deep sequencing of hippocampal neuropil coupled with Nanostring analysis and high-resolution fluorescent in situ hybridisation, estimated the number of distally localised mRNAs in dendrites to be around 2500 [ 75 ].…”

Synaptically-targeted long non-coding RNA SLAMR promotes structural plasticity by increasing translation and CaMKII activity

“…Considering the relative abundance (with CaMKIIα being highly expressed compared to SLAMR), we speculated that SLAMR might play a role in mediating the activity of CaMKIIα in dendrites. Previous studies demonstrated that CaMKIIα is localized in dendrites and translocated to spines in response to neuronal activity 76 – 78 . Consistent with a role in modulating CaMKII activity, we observed that the loss of SLAMR function resulted in a reduction in the active pool of CaMKIIα (T282 phosphorylated) in synaptoneurosomes.…”