Membrane resonance and its ionic mechanisms in rat subthalamic nucleus neurons

The oscillatory activity in the basal ganglia is believed to have an important function, but little is known about its actual mechanisms. We studied the resonance characteristics of subthalamic nucleus (STN) neurons and their ionic mechanisms using whole-cell patch-clamp recordings in rat brain slices. A swept-sine-wave current with constant amplitude and linearly increasing frequency was applied to measure the resonance frequency (f(res)) of STN neurons. We also used single-frequency sine wave current to evoke firing. We found that the resonance of STN neurons was temperature- and voltage-dependent. The f(res) of STN neurons was about 4Hz when the temperature was maintained at 38°C and holding potential was at -70mV. The f(res) increased with more negative holding potentials and decreased with lower temperature. Action potentials fired most readily when the input frequency was near f(res). After application of drug ZD7288 (20μM), the resonance of STN neurons was blocked and the spikes evoked by both impedance amplitude profile (ZAP) current and single-frequency sine wave current arose readily at the lowest frequencies, indicating that hyperpolarization-activated cation current (I(h)) generated the resonance and mediated a preferential coupling at frequencies near f(res) between inputs and firing. In conclusion, there is a θ-frequency resonance mediated by I(h) in STN neurons. The resonance characteristics are temperature- and voltage-dependent. The resonance mediates a frequency-selective coupling between inputs and firing.