title: Targeting of ribosomal protein S6 to dendritic spines by in vivo high frequency stimulation to induce long-term potentiation in the dentate gyrus.
abstract: Late 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.
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, MITILS, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Honcho 4-1-8, Kawaguchi 332-0012, Japan.
authors.forename: Itsuko
authors.initials: I
authors.lastname: Nihonmatsu
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, MITILS, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Honcho 4-1-8, Kawaguchi 332-0012, Japan Department of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohkawa
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, MITILS, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Honcho 4-1-8, Kawaguchi 332-0012, Japan Department of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Saitoh
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, MITILS, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Honcho 4-1-8, Kawaguchi 332-0012, Japan Department of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan inokuchi@med.u-toyama.ac.jp.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inokuchi
keywords: Dendritic spine; Hippocampus; Local protein synthesis; Long-term potentiation (LTP); Ribosomal protein S6