Theta-frequency membrane resonance and its ionic mechanisms in rat subicular pyramidal neurons

The neuron population of the hippocampal formation exhibits oscillatory activity within the theta (theta) frequency band (4-10 Hz), and the intrinsic resonance properties of individual hippocampal neurons contribute to this network oscillation. The subiculum is the pivotal output region of the hippocampal formation and it is involved in many of the physiological and pathological functions of the limbic system. To study the characteristics and underlying mechanisms of resonance activity in subicular pyramidal neurons, we performed whole-cell patch-clamp recordings from these neurons in rat horizontal brain slices. We applied sinusoidal currents with constant amplitudes and linearly increasing frequencies to measure the resonance frequency of subicular pyramidal neurons. We found that the resonance frequency of subicular pyramidal neurons was about 2 Hz at room temperature and 4-6 Hz at 32-35 degrees C. The resonance frequency increased at hyperpolarized membrane potentials and decreased at depolarized membrane potentials. We also investigated three sub-threshold currents involved in the resonance: a slow hyperpolarization-activated cation current; an instantaneously activating, inwardly rectifying potassium current; and an inwardly persistent sodium current. The application of ZD7288 abolished the resonance hump, indicating that hyperpolarization-activated cation current generated resonance. The application of Ba(2+) enlarged the resonance hump at hyperpolarized potentials below -80 mV, indicating that inwardly rectifying potassium current attenuated resonance. The application of TTX suppressed the resonance at depolarized potentials, indicating that persistent sodium current amplified resonance when neurons were depolarized. Thus, there is a theta-frequency resonance mediated by hyperpolarization-activated cation current in subicular pyramidal neurons. This theta-frequency resonance of individual subicular pyramidal neurons may participate in the population's theta oscillation and contribute to the functions of the subiculum.