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: Passive membrane properties, and sag and rebound potentials are genotype-independent. Passive subthreshold membrane properties of CA1-PNs were recorded from 13 slices from nine WT mice and 10 slices from nine DISC1tr mice of 3–4 months of age. There was no difference in the RMP recorded in the first minute after gaining whole cell access (Fig.1B, Table1; WT −80.0 ± 1.0 mV; DISC1 −80.5 ± 0.8 mV; P = 0.7; unpaired, two-tailed Student’s t test; n = 19 WT and 23 DISC1tr CA1-PNs). Because other passive membrane properties including Ri, membrane time constant (τM) and sag upon hyperpolarization exhibit some voltage-dependence, after determination of RMP, CA1-PNs were held at a set pre-stimulus membrane potential of −80 mV by employing an appropriate level of steady-state current injection. A 500-ms, 100-pA hyperpolarizing square-wave current injection step was then applied. The mean voltage responses to this stimulus obtained from the two genotypes are shown in Fig.1A. From such voltage responses we extracted five additional measurements on a cell by cell basis (see Kerrigan et al., 2013). Of these, the Shapiro–Wilk test for normality indicated that RMP, τM and percentage sag measurements were normally distributed, whereas Ri, negative peak and rebound were not normally distributed (Ri WT P < 0.05, DISC1 P < 0.001; negative peak WT P < 0.05, DISC1 P < 0.001; rebound WT P < 0.05, DISC1 P < 0.001). Comparison of these measures between genotypes using appropriate statistical tests (unpaired, two-tailed Student’s t test for normally distributed data, and independent samples Mann–Whitney U test for non-normally distributed data) revealed no genotype-related differences in any of these subthreshold passive membrane properties (Fig.1B, Table1).
Affiliation: School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.