Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1.
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.
Affiliation: School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.Show MeSH
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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.
Affiliation: School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.