Abstract
Local protein synthesis in dendrites contributes to the synaptic modifications underlying learning and memory. The mRNA encoding the α subunit of the calcium/calmodulin dependent Kinase II (CaMKIIα) is dendritically localized and locally translated. A role for CaMKIIα local translation in hippocampus-dependent memory has been demonstrated in mice with disrupted CaMKIIα dendritic translation, through deletion of CaMKIIα 3′UTR. We studied the dendritic localization and local translation of CaMKIIα in the mouse olfactory bulb (OB), the first relay of the olfactory pathway, which exhibits a high level of plasticity in response to olfactory experience. CaMKIIα is expressed by granule cells (GCs) of the OB. Through in situ hybridization and synaptosome preparation, we show that CaMKIIα mRNA is transported in GC dendrites, synaptically localized and might be locally translated at GC synapses. Increases in the synaptic localization of CaMKIIα mRNA and protein in response to brief exposure to new odors demonstrate that they are activity-dependent processes. The activity-induced dendritic transport of CaMKIIα mRNA can be inhibited by an NMDA receptor antagonist and mimicked by an NMDA receptor agonist. Finally, in mice devoid of CaMKIIα 3′UTR, the dendritic localization of CaMKIIα mRNA is disrupted in the OB and olfactory associative learning is severely impaired. Our studies thus reveal a new functional modality for CaMKIIα local translation, as an essential determinant of olfactory plasticity.
Highlights
Since the seminal observation of polyribosomes localized at the base of dendritic spines [1], local translation in dendrites has been shown to be a major determinant of neuronal plasticity, participating in the synaptic changes that underlie learning and memory [2]
This pattern of immunoreactivity is consistent with previous work [19] and confirms that CaMKIIa is expressed by granule cells (GCs) in the olfactory bulb (OB) and present in both their cell bodies and dendrites
As described before [19], CaMKIIa is not expressed by glutamatergic mitral cells, whereas it is typically associated with glutamatergic synapses in other brain regions
Summary
Since the seminal observation of polyribosomes localized at the base of dendritic spines [1], local translation in dendrites has been shown to be a major determinant of neuronal plasticity, participating in the synaptic changes that underlie learning and memory [2]. To directly test the role of CamKIIa local translation in learning and memory, knocked-in mice were generated, in which CamKIIa 39UTR was replaced by the 39UTR of bovine growth hormone mRNA, a message that is not dendritically localized [17]. These mice display a dramatic reduction of CaMKIIa in PSDs of the hippocampus (HC), a reduction in late-phase long-term potentiation, and impairments of hippocampus-dependent memories. This confirms a role for CaMKIIa local translation in synaptic and behavioral plasticity
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