Membrane potential oscillations in CA1 hippocampal pyramidal neurons in vitro: Intrinsic rhythms and fluctuations entrained by sinusoidal injected current

Abstract

The mechanisms mediating intrinsic and entrained CA1 pyramidal neuron rhythmic membrane potential oscillations were investigated in rat hippocampal slices. Intrinsic oscillations (6-14 Hz, < 10 mV) were evoked by long duration (2 s), depolarizing current pulses in 42% of the cells. Oscillations were also evoked by imposing sinusoidal transmembrane currents at 2, 7, and 14 Hz, adjusted at 7 Hz to imitate the synaptically mediated in vivo 'intracellular theta'. Slow all-or-none events (40 mV, 55 ms) - reminiscent of the rhythmic, high threshold slow spikes observed in vivo - were evoked and entrained by the sine wave current cycles with large, imposed depolarization in 35% of the cells. Intrinsic oscillations were insensitive to Ca2+-free, Co2+ (2 mM) and Mn2+ (2 mM) solutions, but were blocked by tetrodotoxin (TTX; 5 μM), illustrating that they were Na+-mediated. Tetraethylammonium (TEA; 15 mM) unmasked slow all-or-none events (40-50 mV, 20-55 ms) and plateau potentials (40-60 mV, 100-700 ms). Plateaus were Co2+ and Mn2+ resistant and were abolished by TTX, hence suggesting that the underlying persistent conductance was Na+-mediated. Plateaus were entrained one-to-one at all sinusoidal current frequencies in Ca2+-free, TEA + Co2+, or TEA + Mn2+ solutions. However, the high threshold Ca2+ spikes uncovered in TEA + TTX could only follow sinusoidal currents of less than 7 Hz. In conclusion, the high threshold Ca2+ and persistent Na+ conductances coexist in CA1 pyramidal cells. The persistent Na+ conductance mediated the intrinsic oscillations, and fluctuated at all the sine wave current frequencies used. The more sluggish high-threshold Ca2+ conductance exclusively oscillated at frequencies of less than 7 Hz and did not support the intrinsic rhythm. Therefore, the findings suggest that the Na+-mediated oscillations may contribute to the high-frequency, type I, hippocampal theta rhythm present in vivo, whereas the high threshold Ca2+ conductance may take part in the low-frequency, type II rhythm.