SUBTHRESHOLD OSCILLATIONS AND RESONANT-FREQUENCY IN GUINEA-PIG CORTICAL-NEURONS - PHYSIOLOGY AND MODELING

1. Intracellular recordings were made from neurons in slices from guinea-pig frontal cortex. In 50% of the cells, sustained subthreshold voltage oscillations were evoked by long (> 6 s) depolarizing pulses. The peak-to-peak amplitude of these oscillations was less than 5 mV and the frequency was voltage dependent, increasing with depolarization from 4 (near rest) to 20 Hz (at 30 mV depolarization). 2. The impedance-frequency relationship of both oscillating and non-oscillating cells was studied by intracellular injection of sinusoidal current with linearly changing frequency. In most cells, a peak in the impedance magnitude (resonant behaviour) was observed at depolarized levels. The frequency of the peak impedance (peak frequency) increased with depolarization from 3 (near rest) to 15 Hz (at 30 mV depolarization). 3. Application of TTX (10(-6) M) significantly decreased the impedance magnitude near the peak frequency. The subthreshold oscillations, however, as well as the action potentials, were fully blocked by TTX. On the other hand, TEA (15 mm) and Cs+ (5 mar) abolished both the subthreshold oscillations and the resonant behaviour. Replacing Ca2+ with Co2+ (5 mM) or Ni2+ (1 mM) did not abolish the subthreshold oscillations. The peak in the frequency-response curve was only slightly reduced. 4. An isopotential membrane model, consisting of a leak current, a fast persistent sodium current, a slow non-inactivating potassium current (with the kinetics of the M-current) and membrane capacitance, is sufficient to produce both voltage oscillations and resonant behaviour. The kinetics of the K+ current by itself is sufficient to produce resonance behaviour. The Na+ current amplifies the peak impedance magnitude and is essential for the generation of subthreshold oscillation. The model correctly predicted the behaviour of the frequency response before and after TTX and TEE application, as well as the relation between the expected passive impedance and the experimental impedance. 5. We speculate that the tendency of the neurons to generate voltage signals at a certain frequency (as a result of the subthreshold oscillations) and to preferentially respond to inputs arriving at the same frequency (the resonance behaviour) promotes population activity at that preferred frequency.