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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 EPSP and IPSP summation. (A) Mean voltage responses to trains of six stimuli delivered at 5, 10, 20, 50 and 100 Hz from WT (black) and DISC1tr (blue) CA1-PNs. Inset graphs show responses on a larger time scale for clarity. The shaded areas represent the SEM. (B) Absolute amplitudes (i) and amplitudes normalized to the first response (ii) for each EPSP in the train. (C) Amplitude of the IPSP at the end of each train plotted against stimulus frequency. In B and C, data are mean ± SEM. n = 14 WT and 14 DISC1tr CA1-PNs from nine WT and nine DISC1tr mice.
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fig04: Schaffer collateral EPSP and IPSP summation. (A) Mean voltage responses to trains of six stimuli delivered at 5, 10, 20, 50 and 100 Hz from WT (black) and DISC1tr (blue) CA1-PNs. Inset graphs show responses on a larger time scale for clarity. The shaded areas represent the SEM. (B) Absolute amplitudes (i) and amplitudes normalized to the first response (ii) for each EPSP in the train. (C) Amplitude of the IPSP at the end of each train plotted against stimulus frequency. In B and C, data are mean ± SEM. n = 14 WT and 14 DISC1tr CA1-PNs from nine WT and nine DISC1tr mice.

Mentions: The relationship between synaptic response and stimulus frequency was examined for short stimulus trains. The group mean voltage responses from both genotypes, at each stimulus frequency tested, are shown in Fig.4A. To examine EPSPs, the peak level of positivity following each stimulus was measured relative to pre-stimulus baseline membrane potential, which was set to −80 mV using appropriate steady-state current injection. Figure4B shows that at all frequencies tested, EPSPs summated throughout the trains [presented as both absolute amplitudes (Fig.4Bi) and normalized to the amplitude of the first EPSP in each train (Fig.4Bii)]. Summation was greater at higher frequencies but also more variable. A trend toward decreased EPSP summation in DISC1tr CA1-PNs was observed at 50 and 100 Hz, but this was not significantly different from WT CA1-PNs (Fig.4B; 100-Hz normalized amplitudes F = 0.9, P = 0.3; repeated-measures anova; n = 14 WT and 14 DISC1tr CA1-PNs).


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 EPSP and IPSP summation. (A) Mean voltage responses to trains of six stimuli delivered at 5, 10, 20, 50 and 100 Hz from WT (black) and DISC1tr (blue) CA1-PNs. Inset graphs show responses on a larger time scale for clarity. The shaded areas represent the SEM. (B) Absolute amplitudes (i) and amplitudes normalized to the first response (ii) for each EPSP in the train. (C) Amplitude of the IPSP at the end of each train plotted against stimulus frequency. In B and C, data are mean ± SEM. n = 14 WT and 14 DISC1tr CA1-PNs from nine WT and nine DISC1tr mice.
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fig04: Schaffer collateral EPSP and IPSP summation. (A) Mean voltage responses to trains of six stimuli delivered at 5, 10, 20, 50 and 100 Hz from WT (black) and DISC1tr (blue) CA1-PNs. Inset graphs show responses on a larger time scale for clarity. The shaded areas represent the SEM. (B) Absolute amplitudes (i) and amplitudes normalized to the first response (ii) for each EPSP in the train. (C) Amplitude of the IPSP at the end of each train plotted against stimulus frequency. In B and C, data are mean ± SEM. n = 14 WT and 14 DISC1tr CA1-PNs from nine WT and nine DISC1tr mice.
Mentions: The relationship between synaptic response and stimulus frequency was examined for short stimulus trains. The group mean voltage responses from both genotypes, at each stimulus frequency tested, are shown in Fig.4A. To examine EPSPs, the peak level of positivity following each stimulus was measured relative to pre-stimulus baseline membrane potential, which was set to −80 mV using appropriate steady-state current injection. Figure4B shows that at all frequencies tested, EPSPs summated throughout the trains [presented as both absolute amplitudes (Fig.4Bi) and normalized to the amplitude of the first EPSP in each train (Fig.4Bii)]. Summation was greater at higher frequencies but also more variable. A trend toward decreased EPSP summation in DISC1tr CA1-PNs was observed at 50 and 100 Hz, but this was not significantly different from WT CA1-PNs (Fig.4B; 100-Hz normalized amplitudes F = 0.9, P = 0.3; repeated-measures anova; n = 14 WT and 14 DISC1tr CA1-PNs).

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