It is interesting to note that Li had a ‘dual’ effect on the cells. It both reduced the amplitude of the fast AHP and broadened the spike, making the cells less excitable, but it also caused the sodium channels to open at a less depolarized potential, making the cells more excitable. We hypothesize that this may be the way in which Li has a dual action of improving both depression and mania. The significance of the effect on the types of cells (LR vs NR) depends on their initial properties. The significant changes that occurred in the action potential shape of LR neurons (broadening of the spike and reduction of the fast AHP amplitude; Supplementary Figures 3d and e) generally reduced excitability in neurons, whereas the significant changes in the NR neurons after Li treatment contributed in a different direction to cell excitability (spike broadening decreased excitability, whereas lowering the threshold increased excitability; Supplementary Figures 3k and m).
