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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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Basal synaptic transmission, paired-pulse profiles and LTP in the temporoammonic pathway. (A) Input–output relationships. n = 26 WT and 20 DISC1tr slices. (B) Paired-pulse profiles. n = 12 WT and 9 DISC1tr slices. (C) TBS-induced LTP. Representative traces from baseline (a), immediately post-TBS (b) and 60 min post-TBS (c) are shown in Ci for WT (black) and DISC1tr (blue) slices. Time-course of fEPSP amplitude following TBS is shown in Cii. (Di) Representative traces showing responses to the TBS protocol for WT (black) and DISC1tr (blue). The four sweeps are superimposed [first sweep (lightest trace) to last sweep (darkest trace)]. (Dii) Area below baseline for each of the four sweeps during the TBS protocol. Data are mean ± SEM. *P < 0.05; unpaired, two-tailed Student’s t test; n = 13 WT and 11 DISC1tr slices.
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fig08: Basal synaptic transmission, paired-pulse profiles and LTP in the temporoammonic pathway. (A) Input–output relationships. n = 26 WT and 20 DISC1tr slices. (B) Paired-pulse profiles. n = 12 WT and 9 DISC1tr slices. (C) TBS-induced LTP. Representative traces from baseline (a), immediately post-TBS (b) and 60 min post-TBS (c) are shown in Ci for WT (black) and DISC1tr (blue) slices. Time-course of fEPSP amplitude following TBS is shown in Cii. (Di) Representative traces showing responses to the TBS protocol for WT (black) and DISC1tr (blue). The four sweeps are superimposed [first sweep (lightest trace) to last sweep (darkest trace)]. (Dii) Area below baseline for each of the four sweeps during the TBS protocol. Data are mean ± SEM. *P < 0.05; unpaired, two-tailed Student’s t test; n = 13 WT and 11 DISC1tr slices.

Mentions: In the TA pathway, fEPSPs were smaller and required stronger stimulation to elicit responses than in the SC pathway. Slope measurements of TA fEPSPs were very variable, probably due to the small size of the responses, and so only fEPSP amplitude data are described below. Similar to the SC pathway, input–output curves in the TA pathway revealed no difference in basal synaptic transmission between WT and DISC1tr slices (Fig.8A; F = 0.2, P = 0.7; repeated-measures anova; n = 26 WT and 20 DISC1tr slices). Analysis of paired-pulse fEPSP amplitudes with respect to baseline showed a bell-shaped relationship with facilitation at all stimulation intervals and greatest facilitation at a stimulus interval of 30 ms (Fig.8B). Cross-genotype comparisons showed no difference in paired-pulse profiles, suggesting that presynaptic glutamate release is also not altered at TA-CA1 synapses by transgenic expression of DISC1tr (fEPSP2/fEPSP1F = 0.004, P = 0.9; repeated-measures anova; n = 12 WT and 9 DISC1tr slices).


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)

Basal synaptic transmission, paired-pulse profiles and LTP in the temporoammonic pathway. (A) Input–output relationships. n = 26 WT and 20 DISC1tr slices. (B) Paired-pulse profiles. n = 12 WT and 9 DISC1tr slices. (C) TBS-induced LTP. Representative traces from baseline (a), immediately post-TBS (b) and 60 min post-TBS (c) are shown in Ci for WT (black) and DISC1tr (blue) slices. Time-course of fEPSP amplitude following TBS is shown in Cii. (Di) Representative traces showing responses to the TBS protocol for WT (black) and DISC1tr (blue). The four sweeps are superimposed [first sweep (lightest trace) to last sweep (darkest trace)]. (Dii) Area below baseline for each of the four sweeps during the TBS protocol. Data are mean ± SEM. *P < 0.05; unpaired, two-tailed Student’s t test; n = 13 WT and 11 DISC1tr slices.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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fig08: Basal synaptic transmission, paired-pulse profiles and LTP in the temporoammonic pathway. (A) Input–output relationships. n = 26 WT and 20 DISC1tr slices. (B) Paired-pulse profiles. n = 12 WT and 9 DISC1tr slices. (C) TBS-induced LTP. Representative traces from baseline (a), immediately post-TBS (b) and 60 min post-TBS (c) are shown in Ci for WT (black) and DISC1tr (blue) slices. Time-course of fEPSP amplitude following TBS is shown in Cii. (Di) Representative traces showing responses to the TBS protocol for WT (black) and DISC1tr (blue). The four sweeps are superimposed [first sweep (lightest trace) to last sweep (darkest trace)]. (Dii) Area below baseline for each of the four sweeps during the TBS protocol. Data are mean ± SEM. *P < 0.05; unpaired, two-tailed Student’s t test; n = 13 WT and 11 DISC1tr slices.
Mentions: In the TA pathway, fEPSPs were smaller and required stronger stimulation to elicit responses than in the SC pathway. Slope measurements of TA fEPSPs were very variable, probably due to the small size of the responses, and so only fEPSP amplitude data are described below. Similar to the SC pathway, input–output curves in the TA pathway revealed no difference in basal synaptic transmission between WT and DISC1tr slices (Fig.8A; F = 0.2, P = 0.7; repeated-measures anova; n = 26 WT and 20 DISC1tr slices). Analysis of paired-pulse fEPSP amplitudes with respect to baseline showed a bell-shaped relationship with facilitation at all stimulation intervals and greatest facilitation at a stimulus interval of 30 ms (Fig.8B). Cross-genotype comparisons showed no difference in paired-pulse profiles, suggesting that presynaptic glutamate release is also not altered at TA-CA1 synapses by transgenic expression of DISC1tr (fEPSP2/fEPSP1F = 0.004, P = 0.9; repeated-measures anova; n = 12 WT and 9 DISC1tr slices).

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