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Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1.

Booth CA, Brown JT, Randall AD - Eur. J. Neurosci. (2014)

Bottom Line: Patch-clamp analysis of synaptic responses in the Schaffer collateral commissural (SC) pathway indicated no genotype-dependence of paired pulse facilitation, excitatory postsynaptic potential summation or AMPA/NMDA ratio.Extracellular recordings also revealed an absence of changes to SC synaptic responses and indicated input-output and short-term plasticity were also unaltered in the temporoammonic (TA) input.These data demonstrate that expressing a truncated form of DISC1 affects intrinsic properties of CA1-PNs and produces pathway-specific effects on long-term synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.

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Schaffer collateral NMDA/AMPA ratios are genotype-independent. (A) Peak amplitude and slope measurements for input–output curves recorded at −80 mV. (B) Paired-pulse ratios recorded at −80 mV. (C) Mean traces from all cells showing where measurements of AMPA and NMDA receptor activation were made. (D) Mean traces from a subset of cells treated with 50 μm D-AP5 (n = 4 WT and n = 5 DISC1 CA1-PNs). (E) Effect of D-AP5 on EPSC peak recorded at −80 mV shows that NMDA receptors make a small contribution to the peak at this membrane potential (n = 4 WT and n = 5 DISC1 CA1-PNs). (F) NMDA/AMPA ratios from all cells, and cells treated with 50 μm D-AP5 which abolishes the NMDA component. Data in A, B, E and F are mean ± SEM. In C and D, the shaded areas represent the SEM. n = 16 WT and 17 DISC1tr CA1-PNs from five WT and six DISC1tr mice.
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fig05: Schaffer collateral NMDA/AMPA ratios are genotype-independent. (A) Peak amplitude and slope measurements for input–output curves recorded at −80 mV. (B) Paired-pulse ratios recorded at −80 mV. (C) Mean traces from all cells showing where measurements of AMPA and NMDA receptor activation were made. (D) Mean traces from a subset of cells treated with 50 μm D-AP5 (n = 4 WT and n = 5 DISC1 CA1-PNs). (E) Effect of D-AP5 on EPSC peak recorded at −80 mV shows that NMDA receptors make a small contribution to the peak at this membrane potential (n = 4 WT and n = 5 DISC1 CA1-PNs). (F) NMDA/AMPA ratios from all cells, and cells treated with 50 μm D-AP5 which abolishes the NMDA component. Data in A, B, E and F are mean ± SEM. In C and D, the shaded areas represent the SEM. n = 16 WT and 17 DISC1tr CA1-PNs from five WT and six DISC1tr mice.

Mentions: Changes in AMPA and/or NMDA receptor activation could contribute to differences in EPSP summation. As there was a trend towards decreased SC EPSP summation in DISC1tr CA1-PNs, voltage-clamp recordings were used to investigate AMPA and NMDA receptor-mediated currents in the SC pathway. As described in the Methods, these recordings were made with Cs+-based pipette solutions and in the presence of gabazine, a selective GABAA receptor antagonist. Input–output curves were recorded at −80 mV and consequently mainly represent activation of AMPA receptors. The input–output relationships of peak amplitude and slope of EPSCs were unaffected by genotype (Fig.5A; amplitude F = 0.002, P = 1; slope F = 1.0, P = 0.3; repeated-measures anova; n = 23 WT and 23 DISC1tr CA1-PNs) suggesting that AMPA receptor activation is not altered in DISC1tr CA1-PNs compared with WT. Paired-pulse profiles for EPSCs were also constructed at −80 mV, and facilitation was seen at pulse intervals shorter than 100 ms as shown in Fig.5B. Again, there was no effect of genotype on the paired-pulse profiles (F = 2.8, P = 0.1; repeated-measures anova; n = 20 WT and 19 DISC1tr CA1-PNs) suggesting that presynaptic glutamate release probability is also unaffected by genotype.


Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1.

Booth CA, Brown JT, Randall AD - Eur. J. Neurosci. (2014)

Schaffer collateral NMDA/AMPA ratios are genotype-independent. (A) Peak amplitude and slope measurements for input–output curves recorded at −80 mV. (B) Paired-pulse ratios recorded at −80 mV. (C) Mean traces from all cells showing where measurements of AMPA and NMDA receptor activation were made. (D) Mean traces from a subset of cells treated with 50 μm D-AP5 (n = 4 WT and n = 5 DISC1 CA1-PNs). (E) Effect of D-AP5 on EPSC peak recorded at −80 mV shows that NMDA receptors make a small contribution to the peak at this membrane potential (n = 4 WT and n = 5 DISC1 CA1-PNs). (F) NMDA/AMPA ratios from all cells, and cells treated with 50 μm D-AP5 which abolishes the NMDA component. Data in A, B, E and F are mean ± SEM. In C and D, the shaded areas represent the SEM. n = 16 WT and 17 DISC1tr CA1-PNs from five WT and six DISC1tr mice.
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Related In: Results  -  Collection

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fig05: Schaffer collateral NMDA/AMPA ratios are genotype-independent. (A) Peak amplitude and slope measurements for input–output curves recorded at −80 mV. (B) Paired-pulse ratios recorded at −80 mV. (C) Mean traces from all cells showing where measurements of AMPA and NMDA receptor activation were made. (D) Mean traces from a subset of cells treated with 50 μm D-AP5 (n = 4 WT and n = 5 DISC1 CA1-PNs). (E) Effect of D-AP5 on EPSC peak recorded at −80 mV shows that NMDA receptors make a small contribution to the peak at this membrane potential (n = 4 WT and n = 5 DISC1 CA1-PNs). (F) NMDA/AMPA ratios from all cells, and cells treated with 50 μm D-AP5 which abolishes the NMDA component. Data in A, B, E and F are mean ± SEM. In C and D, the shaded areas represent the SEM. n = 16 WT and 17 DISC1tr CA1-PNs from five WT and six DISC1tr mice.
Mentions: Changes in AMPA and/or NMDA receptor activation could contribute to differences in EPSP summation. As there was a trend towards decreased SC EPSP summation in DISC1tr CA1-PNs, voltage-clamp recordings were used to investigate AMPA and NMDA receptor-mediated currents in the SC pathway. As described in the Methods, these recordings were made with Cs+-based pipette solutions and in the presence of gabazine, a selective GABAA receptor antagonist. Input–output curves were recorded at −80 mV and consequently mainly represent activation of AMPA receptors. The input–output relationships of peak amplitude and slope of EPSCs were unaffected by genotype (Fig.5A; amplitude F = 0.002, P = 1; slope F = 1.0, P = 0.3; repeated-measures anova; n = 23 WT and 23 DISC1tr CA1-PNs) suggesting that AMPA receptor activation is not altered in DISC1tr CA1-PNs compared with WT. Paired-pulse profiles for EPSCs were also constructed at −80 mV, and facilitation was seen at pulse intervals shorter than 100 ms as shown in Fig.5B. Again, there was no effect of genotype on the paired-pulse profiles (F = 2.8, P = 0.1; repeated-measures anova; n = 20 WT and 19 DISC1tr CA1-PNs) suggesting that presynaptic glutamate release probability is also unaffected by genotype.

Bottom Line: Patch-clamp analysis of synaptic responses in the Schaffer collateral commissural (SC) pathway indicated no genotype-dependence of paired pulse facilitation, excitatory postsynaptic potential summation or AMPA/NMDA ratio.Extracellular recordings also revealed an absence of changes to SC synaptic responses and indicated input-output and short-term plasticity were also unaltered in the temporoammonic (TA) input.These data demonstrate that expressing a truncated form of DISC1 affects intrinsic properties of CA1-PNs and produces pathway-specific effects on long-term synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.

Show MeSH
Related in: MedlinePlus