Abstract
ABSTRACTLate phase long-term potentiation (L-LTP) in the hippocampus is believed to be the cellular basis of long-term memory. Protein synthesis is required for persistent forms of synaptic plasticity, including L-LTP. Neural activity is thought to enhance local protein synthesis in dendrites, and one of the mechanisms required to induce or maintain the long-lasting synaptic plasticity is protein translation in the dendrites. One regulator of translational processes is ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit. Although polyribosomes containing rpS6 are observed in dendritic spines, it remains unclear whether L-LTP induction triggers selective targeting of the translational machinery to activated synapses in vivo. Therefore, we investigated synaptic targeting of the translational machinery by observing rpS6 immunoreactivity during high frequency stimulation (HFS) for L-LTP induction in vivo. Immunoelectron microscopic analysis revealed a selective but transient increase in rpS6 immunoreactivity occurring as early as 15 min after the onset of HFS in dendritic spine heads at synaptic sites receiving HFS. Concurrently, levels of the rpS6 protein rapidly declined in somata of granule cells, as determined using immunofluorescence microscopy. These results suggest that the translational machinery is rapidly targeted to activated spines and that this targeting mechanism may contribute to the establishment of L-LTP.
Highlights
New protein synthesis mediated by neural activity is an essential process for long-lasting neuronal plasticity
Late phase long-term potentiation (L-Long-term potentiation (LTP))-inducing high frequency stimulation (HFS) rapidly and increases F-actin content in the stimulated layers We previously reported that HFS(500)-induced L-LTP in the dentate gyrus of freely moving rats is associated with the reorganization of the actin cytoskeleton, characterized by a longlasting increase in F-actin content within the LTP-induced layer (Fukazawa et al, 2003; Ohkawa et al, 2012)
The increase in F-actin levels was observed from 45 min to several weeks after the onset of HFS, suggesting that this increase is important in the late phase of LTP (Fukazawa et al, 2003)
Summary
New protein synthesis mediated by neural activity is an essential process for long-lasting neuronal plasticity. In vitro studies revealed that polyribosomes are selectively increased in spines during LTP in the CA1 region of slices prepared from the developing and mature hippocampus (Bourne et al, 2007; Ostroff et al, 2002). It remains unclear whether LTP induction in vivo triggers the selective targeting of the translational machinery to activated sites, and whether the selective targeting is directed by stimulation inducing LTP in hippocampal areas outside the CA1 region
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