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Differentiation in the protein synthesis-dependency of persistent synaptic plasticity in mossy fiber and associational/commissural CA3 synapses in vivo.

Hagena H, Manahan-Vaughan D - Front Integr Neurosci (2013)

Bottom Line: In contrast, at AC-CA3 synapses, translation inhibitors prevented intermediate/late-LTP and late-LTD only.Transcription effects were also synapse-specific: whereas transcription inhibitors inhibited late-LTP and late-LTD (>3 h) at mf-CA3 synapses, at AC-CA3 synapses, protein transcription affected early-LTP and late-LTD.These results show that the AC-CA3 and mf-CA3 synapses display different properties in terms of their protein synthesis dependency, suggesting different roles in the processing of short- and long term synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurophysiology, Medical Faculty, Ruhr University Bochum Bochum, Germany ; International Graduate School for Neuroscience, Ruhr University Bochum Bochum, Germany.

ABSTRACT
Long-term potentiation (LTP) and long-term depression (LTD) are two mechanisms involved in the long-term storage of information in hippocampal synapses. In the hippocampal CA1 region, the late phases of LTP and LTD are protein-synthesis dependent. In the dentate gyrus, late-LTP but not LTD requires protein synthesis. The protein synthesis-dependency of persistent plasticity at CA3 synapses has not yet been characterized. Here, the roles of protein transcription and translation at mossy fiber (mf) and associational/commissural (AC)- synapses were studied in freely behaving rats. In control animals, low-frequency stimulation (LFS) evoked robust LTD (>24 h), whereas high-frequency stimulation (HFS) elicited robust LTP (>24 h) at both mf-CA3 and AC-CA3 synapses. Translation inhibitors prevented early and late phases of LTP and LTD at mf-CA3 synapses. In contrast, at AC-CA3 synapses, translation inhibitors prevented intermediate/late-LTP and late-LTD only. Transcription effects were also synapse-specific: whereas transcription inhibitors inhibited late-LTP and late-LTD (>3 h) at mf-CA3 synapses, at AC-CA3 synapses, protein transcription affected early-LTP and late-LTD. These results show that the AC-CA3 and mf-CA3 synapses display different properties in terms of their protein synthesis dependency, suggesting different roles in the processing of short- and long term synaptic plasticity.

No MeSH data available.


Related in: MedlinePlus

Inhibitors of transcription affect only the late phase of long-term synaptic plasticity at mossy fiber–CA3 synapses. (A) In vehicle-injected animals, application of HFS facilitates LTP. When animals are treated with actinomycin D (72 μg) an inhibition of the late phase of LTP occurs. (B) LFS elicits LTD in vehicle-injected animals. Application of actinomycin D inhibits the late phase of LTD. (C) HFS (4 trains of 100 pulses given at 100 Hz) results in LTP. Injection of the transcription inhibitor DRB (20 nM) inhibits the late phase of LTP. (D) In control groups, stimulation with 900 pulses at 1 Hz (LFS) elicits LTD. Injection of DRB inhibits the late phase of LTD. Line breaks indicate change in time scale. (E) Analog traces in the left panel were recorded (i) pre-HFS, (ii) 5 min post-HFS, and (iii) 24 h HFS in the presence of vehicle (upper traces) or actinomycin D (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. Analog traces in the right panel represent recordings taken (i) pre-LFS, (ii) 5 min post-LFS, and (iii) 24 h post-LFS in the presence of vehicle (upper traces) or Actinomycin D (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. (F) Analog traces in the left panel represent fEPSP responses obtained (i) pre-HFS, (ii) 5 min post-HFS, and (iii) 24 h post-HFS in the presence of vehicle (upper traces) or DRB (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. Analog traces in the right panel represent recordings taken (i) pre-LFS, (ii) 5 min post-LFS, and (iii) 24 h post-LFS in the presence of vehicle (upper traces) or DRB (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms.
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Figure 3: Inhibitors of transcription affect only the late phase of long-term synaptic plasticity at mossy fiber–CA3 synapses. (A) In vehicle-injected animals, application of HFS facilitates LTP. When animals are treated with actinomycin D (72 μg) an inhibition of the late phase of LTP occurs. (B) LFS elicits LTD in vehicle-injected animals. Application of actinomycin D inhibits the late phase of LTD. (C) HFS (4 trains of 100 pulses given at 100 Hz) results in LTP. Injection of the transcription inhibitor DRB (20 nM) inhibits the late phase of LTP. (D) In control groups, stimulation with 900 pulses at 1 Hz (LFS) elicits LTD. Injection of DRB inhibits the late phase of LTD. Line breaks indicate change in time scale. (E) Analog traces in the left panel were recorded (i) pre-HFS, (ii) 5 min post-HFS, and (iii) 24 h HFS in the presence of vehicle (upper traces) or actinomycin D (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. Analog traces in the right panel represent recordings taken (i) pre-LFS, (ii) 5 min post-LFS, and (iii) 24 h post-LFS in the presence of vehicle (upper traces) or Actinomycin D (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. (F) Analog traces in the left panel represent fEPSP responses obtained (i) pre-HFS, (ii) 5 min post-HFS, and (iii) 24 h post-HFS in the presence of vehicle (upper traces) or DRB (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. Analog traces in the right panel represent recordings taken (i) pre-LFS, (ii) 5 min post-LFS, and (iii) 24 h post-LFS in the presence of vehicle (upper traces) or DRB (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms.

Mentions: To elucidate the effect of transcriptional inhibitors on protein-synthesis at mf-CA3 synapses, actinomycin D and DRB were used. Application of actinomycin D 2 h before HFS or LFS resulted in an inhibition of late-LTP (Figures 3A,E) or late-LTD (Figures 3B,E), respectively, compared to controls (ANOVA, F(1, 8) = 5.63; p = 0.04; interaction effect: p = 0.16; n = 6 and ANOVA, F(1, 8) = 6.7; p = 0.03; interaction effect: p = 0.06; n = 6).


Differentiation in the protein synthesis-dependency of persistent synaptic plasticity in mossy fiber and associational/commissural CA3 synapses in vivo.

Hagena H, Manahan-Vaughan D - Front Integr Neurosci (2013)

Inhibitors of transcription affect only the late phase of long-term synaptic plasticity at mossy fiber–CA3 synapses. (A) In vehicle-injected animals, application of HFS facilitates LTP. When animals are treated with actinomycin D (72 μg) an inhibition of the late phase of LTP occurs. (B) LFS elicits LTD in vehicle-injected animals. Application of actinomycin D inhibits the late phase of LTD. (C) HFS (4 trains of 100 pulses given at 100 Hz) results in LTP. Injection of the transcription inhibitor DRB (20 nM) inhibits the late phase of LTP. (D) In control groups, stimulation with 900 pulses at 1 Hz (LFS) elicits LTD. Injection of DRB inhibits the late phase of LTD. Line breaks indicate change in time scale. (E) Analog traces in the left panel were recorded (i) pre-HFS, (ii) 5 min post-HFS, and (iii) 24 h HFS in the presence of vehicle (upper traces) or actinomycin D (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. Analog traces in the right panel represent recordings taken (i) pre-LFS, (ii) 5 min post-LFS, and (iii) 24 h post-LFS in the presence of vehicle (upper traces) or Actinomycin D (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. (F) Analog traces in the left panel represent fEPSP responses obtained (i) pre-HFS, (ii) 5 min post-HFS, and (iii) 24 h post-HFS in the presence of vehicle (upper traces) or DRB (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. Analog traces in the right panel represent recordings taken (i) pre-LFS, (ii) 5 min post-LFS, and (iii) 24 h post-LFS in the presence of vehicle (upper traces) or DRB (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms.
© Copyright Policy - open-access
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Figure 3: Inhibitors of transcription affect only the late phase of long-term synaptic plasticity at mossy fiber–CA3 synapses. (A) In vehicle-injected animals, application of HFS facilitates LTP. When animals are treated with actinomycin D (72 μg) an inhibition of the late phase of LTP occurs. (B) LFS elicits LTD in vehicle-injected animals. Application of actinomycin D inhibits the late phase of LTD. (C) HFS (4 trains of 100 pulses given at 100 Hz) results in LTP. Injection of the transcription inhibitor DRB (20 nM) inhibits the late phase of LTP. (D) In control groups, stimulation with 900 pulses at 1 Hz (LFS) elicits LTD. Injection of DRB inhibits the late phase of LTD. Line breaks indicate change in time scale. (E) Analog traces in the left panel were recorded (i) pre-HFS, (ii) 5 min post-HFS, and (iii) 24 h HFS in the presence of vehicle (upper traces) or actinomycin D (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. Analog traces in the right panel represent recordings taken (i) pre-LFS, (ii) 5 min post-LFS, and (iii) 24 h post-LFS in the presence of vehicle (upper traces) or Actinomycin D (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. (F) Analog traces in the left panel represent fEPSP responses obtained (i) pre-HFS, (ii) 5 min post-HFS, and (iii) 24 h post-HFS in the presence of vehicle (upper traces) or DRB (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms. Analog traces in the right panel represent recordings taken (i) pre-LFS, (ii) 5 min post-LFS, and (iii) 24 h post-LFS in the presence of vehicle (upper traces) or DRB (lower traces). Vertical scale bar: 2 mV, horizontal scale bar: 8 ms.
Mentions: To elucidate the effect of transcriptional inhibitors on protein-synthesis at mf-CA3 synapses, actinomycin D and DRB were used. Application of actinomycin D 2 h before HFS or LFS resulted in an inhibition of late-LTP (Figures 3A,E) or late-LTD (Figures 3B,E), respectively, compared to controls (ANOVA, F(1, 8) = 5.63; p = 0.04; interaction effect: p = 0.16; n = 6 and ANOVA, F(1, 8) = 6.7; p = 0.03; interaction effect: p = 0.06; n = 6).

Bottom Line: In contrast, at AC-CA3 synapses, translation inhibitors prevented intermediate/late-LTP and late-LTD only.Transcription effects were also synapse-specific: whereas transcription inhibitors inhibited late-LTP and late-LTD (>3 h) at mf-CA3 synapses, at AC-CA3 synapses, protein transcription affected early-LTP and late-LTD.These results show that the AC-CA3 and mf-CA3 synapses display different properties in terms of their protein synthesis dependency, suggesting different roles in the processing of short- and long term synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurophysiology, Medical Faculty, Ruhr University Bochum Bochum, Germany ; International Graduate School for Neuroscience, Ruhr University Bochum Bochum, Germany.

ABSTRACT
Long-term potentiation (LTP) and long-term depression (LTD) are two mechanisms involved in the long-term storage of information in hippocampal synapses. In the hippocampal CA1 region, the late phases of LTP and LTD are protein-synthesis dependent. In the dentate gyrus, late-LTP but not LTD requires protein synthesis. The protein synthesis-dependency of persistent plasticity at CA3 synapses has not yet been characterized. Here, the roles of protein transcription and translation at mossy fiber (mf) and associational/commissural (AC)- synapses were studied in freely behaving rats. In control animals, low-frequency stimulation (LFS) evoked robust LTD (>24 h), whereas high-frequency stimulation (HFS) elicited robust LTP (>24 h) at both mf-CA3 and AC-CA3 synapses. Translation inhibitors prevented early and late phases of LTP and LTD at mf-CA3 synapses. In contrast, at AC-CA3 synapses, translation inhibitors prevented intermediate/late-LTP and late-LTD only. Transcription effects were also synapse-specific: whereas transcription inhibitors inhibited late-LTP and late-LTD (>3 h) at mf-CA3 synapses, at AC-CA3 synapses, protein transcription affected early-LTP and late-LTD. These results show that the AC-CA3 and mf-CA3 synapses display different properties in terms of their protein synthesis dependency, suggesting different roles in the processing of short- and long term synaptic plasticity.

No MeSH data available.


Related in: MedlinePlus