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SCRAPPER regulates the thresholds of long-term potentiation/depression, the bidirectional synaptic plasticity in hippocampal CA3-CA1 synapses.

Takagi H, Setou M, Ito S, Yao I - Neural Plast. (2012)

Bottom Line: SCRAPPER, which is an F-box protein encoded by FBXL20, regulates the frequency of the miniature excitatory synaptic current through the ubiquitination of Rab3-interacting molecule 1.Compared to wild-type mice, Scrapper-knockout mice exhibited LTDs with smaller magnitudes after induction with low-frequency stimulation and LTPs with larger magnitudes after induction with tetanus stimulation.These findings suggest that SCRAPPER regulates the threshold of bidirectional synaptic plasticity and, therefore, metaplasticity.

View Article: PubMed Central - PubMed

Affiliation: Cellular & Molecular Synaptic Function Unit, Initial Research Project, Okinawa Institute of Science and Technology Promotion Corporation, Tancha, Onna, Japan.

ABSTRACT
SCRAPPER, which is an F-box protein encoded by FBXL20, regulates the frequency of the miniature excitatory synaptic current through the ubiquitination of Rab3-interacting molecule 1. Here, we recorded the induction of long-term potentiation/depression (LTP/LTD) in CA3-CA1 synapses in E3 ubiquitin ligase SCRAPPER-deficient hippocampal slices. Compared to wild-type mice, Scrapper-knockout mice exhibited LTDs with smaller magnitudes after induction with low-frequency stimulation and LTPs with larger magnitudes after induction with tetanus stimulation. These findings suggest that SCRAPPER regulates the threshold of bidirectional synaptic plasticity and, therefore, metaplasticity.

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Comparison of the field excitatory postsynaptic potential (fEPSP) slope changes between wild-type (WT) and Scrapper-knockout (SCR-KO) mice at different stimulation frequencies. (a) Means of 10 consecutive sweeps before and after (45–55 min) stimulation. Mean (± SEM) effect of the stimulus of the conditioning stimulation delivered at various frequencies on the response measured 50 min after conditioning (□, WT; ■, SCR-KO) *P < 0.05 (t-test). (b) Schematic model of the long-term potentiation/depression (LTP/LTD) threshold changes in SCR-KO hippocampus and the dependence on stimulus frequency.
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fig3: Comparison of the field excitatory postsynaptic potential (fEPSP) slope changes between wild-type (WT) and Scrapper-knockout (SCR-KO) mice at different stimulation frequencies. (a) Means of 10 consecutive sweeps before and after (45–55 min) stimulation. Mean (± SEM) effect of the stimulus of the conditioning stimulation delivered at various frequencies on the response measured 50 min after conditioning (□, WT; ■, SCR-KO) *P < 0.05 (t-test). (b) Schematic model of the long-term potentiation/depression (LTP/LTD) threshold changes in SCR-KO hippocampus and the dependence on stimulus frequency.

Mentions: Prior synaptic or cellular activity influences the degree or threshold of the subsequent induction of synaptic plasticity, which is a process known as metaplasticity. Next, we compared the threshold of bidirectional synaptic plasticity between the WT and SCR-KO mice. As shown in Figure 3(a), the threshold of bidirectional synaptic plasticity was shifted to the lower frequency area. The schematic model of the LTP/LTD threshold in Figure 3(b) illustrates that the shifts to the lower frequency area in SCR-KO hippocampus depended on stimulus frequency.


SCRAPPER regulates the thresholds of long-term potentiation/depression, the bidirectional synaptic plasticity in hippocampal CA3-CA1 synapses.

Takagi H, Setou M, Ito S, Yao I - Neural Plast. (2012)

Comparison of the field excitatory postsynaptic potential (fEPSP) slope changes between wild-type (WT) and Scrapper-knockout (SCR-KO) mice at different stimulation frequencies. (a) Means of 10 consecutive sweeps before and after (45–55 min) stimulation. Mean (± SEM) effect of the stimulus of the conditioning stimulation delivered at various frequencies on the response measured 50 min after conditioning (□, WT; ■, SCR-KO) *P < 0.05 (t-test). (b) Schematic model of the long-term potentiation/depression (LTP/LTD) threshold changes in SCR-KO hippocampus and the dependence on stimulus frequency.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3539422&req=5

fig3: Comparison of the field excitatory postsynaptic potential (fEPSP) slope changes between wild-type (WT) and Scrapper-knockout (SCR-KO) mice at different stimulation frequencies. (a) Means of 10 consecutive sweeps before and after (45–55 min) stimulation. Mean (± SEM) effect of the stimulus of the conditioning stimulation delivered at various frequencies on the response measured 50 min after conditioning (□, WT; ■, SCR-KO) *P < 0.05 (t-test). (b) Schematic model of the long-term potentiation/depression (LTP/LTD) threshold changes in SCR-KO hippocampus and the dependence on stimulus frequency.
Mentions: Prior synaptic or cellular activity influences the degree or threshold of the subsequent induction of synaptic plasticity, which is a process known as metaplasticity. Next, we compared the threshold of bidirectional synaptic plasticity between the WT and SCR-KO mice. As shown in Figure 3(a), the threshold of bidirectional synaptic plasticity was shifted to the lower frequency area. The schematic model of the LTP/LTD threshold in Figure 3(b) illustrates that the shifts to the lower frequency area in SCR-KO hippocampus depended on stimulus frequency.

Bottom Line: SCRAPPER, which is an F-box protein encoded by FBXL20, regulates the frequency of the miniature excitatory synaptic current through the ubiquitination of Rab3-interacting molecule 1.Compared to wild-type mice, Scrapper-knockout mice exhibited LTDs with smaller magnitudes after induction with low-frequency stimulation and LTPs with larger magnitudes after induction with tetanus stimulation.These findings suggest that SCRAPPER regulates the threshold of bidirectional synaptic plasticity and, therefore, metaplasticity.

View Article: PubMed Central - PubMed

Affiliation: Cellular & Molecular Synaptic Function Unit, Initial Research Project, Okinawa Institute of Science and Technology Promotion Corporation, Tancha, Onna, Japan.

ABSTRACT
SCRAPPER, which is an F-box protein encoded by FBXL20, regulates the frequency of the miniature excitatory synaptic current through the ubiquitination of Rab3-interacting molecule 1. Here, we recorded the induction of long-term potentiation/depression (LTP/LTD) in CA3-CA1 synapses in E3 ubiquitin ligase SCRAPPER-deficient hippocampal slices. Compared to wild-type mice, Scrapper-knockout mice exhibited LTDs with smaller magnitudes after induction with low-frequency stimulation and LTPs with larger magnitudes after induction with tetanus stimulation. These findings suggest that SCRAPPER regulates the threshold of bidirectional synaptic plasticity and, therefore, metaplasticity.

Show MeSH
Related in: MedlinePlus