Paradoxical effects of lithium on field potentials of dentate granule cells in slices of rat hippocampus

The effects of lithium ions (Li +) on evoked field potentials of dentate granule cells were studied in vitro with rat hippocampal slices. Lithium (substituted for choline) reduced the amplitude of the antidromic population spike in a dose-dependent manner; 10 mM Li + had little or no effect, whereas 40 mM strongly reduced the response within 15 min. A paradoxical effect was observed at 25 mM: the antidromic spike was reduced by ~ 50%, but a second population spike frequently appeared. This Li + -induced spike was reversibly blocked by cobalt ions (Co 2+), which suggests that it was caused by calcium ion (Ca 2+) influx. Lithium (25 mM) also consistently reduced the population EPSP to perforant path stimulation, although occasionally a population spike was also induced. These paradoxical effects of Li + on neurons of the mammalian brain can be reconciled with previous observations on simple neuronal systems and may be involved in the therapeutic or toxic effects of LP under clinical conditions.