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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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Related in: MedlinePlus

Long-term potentiation/depression (LTP/LTD) induction by stimulation at different frequencies in wild-type (WT) or Scrapper-knockout (SCR-KO) hippocampal slices. Left column: records of representative experiments in which LTP/LTD was induced. Low-frequency stimulation (LFS, 1 Hz, 900 s) (a), middle-frequency stimulation (MFS, 10 Hz, 90 s) (b), or high-frequency stimulation (HFS, 100 Hz, 1 s) (c) was used as the input. Right column: normalized means (± standard error of the mean (SEM)) of field excitatory postsynaptic potential (fEPSP) slopes from WT or SCR-KO hippocampal slices. Each point represents a single measure of the initial slope of the population excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the Schaffer collaterals at 1/60 Hz. The horizontal bar or the arrow represents the period of stimulation. The number of mice, n = 8, 5, and 4 in (a), (b), and (c), respectively. (◊, WT; ◆, SCR-KO).
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fig2: Long-term potentiation/depression (LTP/LTD) induction by stimulation at different frequencies in wild-type (WT) or Scrapper-knockout (SCR-KO) hippocampal slices. Left column: records of representative experiments in which LTP/LTD was induced. Low-frequency stimulation (LFS, 1 Hz, 900 s) (a), middle-frequency stimulation (MFS, 10 Hz, 90 s) (b), or high-frequency stimulation (HFS, 100 Hz, 1 s) (c) was used as the input. Right column: normalized means (± standard error of the mean (SEM)) of field excitatory postsynaptic potential (fEPSP) slopes from WT or SCR-KO hippocampal slices. Each point represents a single measure of the initial slope of the population excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the Schaffer collaterals at 1/60 Hz. The horizontal bar or the arrow represents the period of stimulation. The number of mice, n = 8, 5, and 4 in (a), (b), and (c), respectively. (◊, WT; ◆, SCR-KO).

Mentions: SCR-KO mice had smaller body sizes than their WT littermates did (Figure 1(a)), and they did not express the SCRAPPER protein (Figure 1(b)). We recorded LTP/LTD induction in hippocampal CA3-CA1 synapses in brain slices of SCR-KO mice. First, we induced extended periods of LFS in the range of 1 Hz in order to yield an LTD. The lasting consequences of 900 pulses that were delivered at 1 Hz are illustrated in Figure 2(a). The responses were often facilitated immediately after the onset of the conditioning stimulation, but during conditioning, the response magnitude always progressively declined to values below the initial baseline (data not shown). When the baseline measurements were resumed (at 1/60 Hz), the first response was always depressed and was even below the value attained during LFS (Figure 2(a)). Although there was usually some recovery in the response magnitude over the next several minutes, the population fEPSP slope always reached a plateau at a value that was significantly depressed compared to the value for the pre-LFS control period (Figure 2(a)).


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)

Long-term potentiation/depression (LTP/LTD) induction by stimulation at different frequencies in wild-type (WT) or Scrapper-knockout (SCR-KO) hippocampal slices. Left column: records of representative experiments in which LTP/LTD was induced. Low-frequency stimulation (LFS, 1 Hz, 900 s) (a), middle-frequency stimulation (MFS, 10 Hz, 90 s) (b), or high-frequency stimulation (HFS, 100 Hz, 1 s) (c) was used as the input. Right column: normalized means (± standard error of the mean (SEM)) of field excitatory postsynaptic potential (fEPSP) slopes from WT or SCR-KO hippocampal slices. Each point represents a single measure of the initial slope of the population excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the Schaffer collaterals at 1/60 Hz. The horizontal bar or the arrow represents the period of stimulation. The number of mice, n = 8, 5, and 4 in (a), (b), and (c), respectively. (◊, WT; ◆, SCR-KO).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539422&req=5

fig2: Long-term potentiation/depression (LTP/LTD) induction by stimulation at different frequencies in wild-type (WT) or Scrapper-knockout (SCR-KO) hippocampal slices. Left column: records of representative experiments in which LTP/LTD was induced. Low-frequency stimulation (LFS, 1 Hz, 900 s) (a), middle-frequency stimulation (MFS, 10 Hz, 90 s) (b), or high-frequency stimulation (HFS, 100 Hz, 1 s) (c) was used as the input. Right column: normalized means (± standard error of the mean (SEM)) of field excitatory postsynaptic potential (fEPSP) slopes from WT or SCR-KO hippocampal slices. Each point represents a single measure of the initial slope of the population excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the Schaffer collaterals at 1/60 Hz. The horizontal bar or the arrow represents the period of stimulation. The number of mice, n = 8, 5, and 4 in (a), (b), and (c), respectively. (◊, WT; ◆, SCR-KO).
Mentions: SCR-KO mice had smaller body sizes than their WT littermates did (Figure 1(a)), and they did not express the SCRAPPER protein (Figure 1(b)). We recorded LTP/LTD induction in hippocampal CA3-CA1 synapses in brain slices of SCR-KO mice. First, we induced extended periods of LFS in the range of 1 Hz in order to yield an LTD. The lasting consequences of 900 pulses that were delivered at 1 Hz are illustrated in Figure 2(a). The responses were often facilitated immediately after the onset of the conditioning stimulation, but during conditioning, the response magnitude always progressively declined to values below the initial baseline (data not shown). When the baseline measurements were resumed (at 1/60 Hz), the first response was always depressed and was even below the value attained during LFS (Figure 2(a)). Although there was usually some recovery in the response magnitude over the next several minutes, the population fEPSP slope always reached a plateau at a value that was significantly depressed compared to the value for the pre-LFS control period (Figure 2(a)).

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