Figure 1.
Hyperexcitability in hippocampal neurons derived from BD patients. A. Cells patched at 4.5 weeks (t2) from start of differentiation. The points represent the mean of each cell line (patient), but the number of total neurons patched is as follows: DG: control 76 neurons, LR 69 neurons, NR 25 neurons; CA3: control 58 neurons, LR 46 neurons, NR 71 neurons. DG BD LR and NR neurons are hyperexcitable when compared to controls, but only BD LR CA3 neurons are hyperexcitable compared to controls. B. Representative recordings in current clamp mode of evoked potentials for a control (blue), C. LR (red) and D. NR (green) neuron. Plotting only the high current injection component reveals that the hyperexcitability of LR neurons was in the form of sustained activity with high current injections, as can be seen from the representative traces of the E. control (blue), F. LR (red) and G. NR (green) CA3 neurons. H. Spontaneous activity. BD LR neurons have an increase in the rate of spontaneous activity both in DG and CA3 neurons. Analysis of spike shape. I. Example recordings of a single spike in current clamp mode of a control (blue) neuron, J. LR (red) neuron and K. NR (green) neuron. L. The fast after-hyperpolarization (AHP) is increased in the BD NR DG neuron at the t2 time point. Our previous report at t* (~3.5 weeks) ~ (14) showed that DG LR fast AHP was also increased at that time point. Fast AHP is also increased in BD LR CA3 neurons. M. Spike amplitude is larger for BD LR neurons, both in DG and CA3, when compared to control and NR neurons. N. Spike width is narrower in CA3 LR neurons. In (14), at the t* time point, DG LR neurons also displayed a narrower spike width. O. The threshold for eliciting an action potential is more depolarized in DG NR neurons (similar to our previous report) compared to control and BD LR neurons, but there is no significant change between the 3 groups in CA3 neurons. P. Input conductance is larger in CA3 BD NR neurons compared to control and BD LR neurons. Asterisks represent statistical significance by the following code: * p value<0.05, **p value<0.01, ***p<0.001, ****p<0.0001. Error bars represent standard error.