Isoflurane attenuates resonant responses of auditory thalamic neurons

Abstract

In thalamocortical neurons, sensory signals are transformed differently during various states of consciousness. We investigated the effects of a general anesthetic, isoflurane, on the frequency responses of neurons in the ventral medial geniculate body, the primary nucleus of the auditory thalamus. Using slice preparations, whole cell current-clamp recording techniques, and frequency-domain analyses with oscillatory inputs, we observed a resonance in the hyperpolarized voltage range, implying a frequency preference near 1 Hz in the subthreshold frequency responses of medial geniculate neurons. As in other thalamocortical neurons, an interaction of a T-type Ca2+ current with passive membrane properties generates the resonant responses. The frequency preference shapes the input-output signal transformation, coupling oscillatory inputs at preferred frequencies to firing. Thus resonance may contribute to the rhythmic synchronization of the output to the cortex. In a concentration range of 0.5-3%, isoflurane application reversibly decreased the resonant responses of medial geniculate neurons. Throughout the subthreshold voltage range, it reduced impedance at frequencies < 10 Hz. At depolarized potentials near -60 mV, isoflurane reduced the low-pass filter selectivity of the neuron membrane. At rest near -70 mV or at hyperpolarized potentials, isoflurane had a greater effect on resonance (centered at approximately 1 Hz), reducing the peak impedance more than the magnitudes at other frequencies. At concentrations of > or = 2%, isoflurane completely blocked the resonance peak, thereby imposing low-pass characteristics of poor quality throughout the subthreshold voltage range. Application of isoflurane reversibly increased membrane conductance and the current threshold for firing evoked by depolarizing pulses from potentials between -60 and -90 mV. The neurons discharged in a tonic pattern on depolarization from about -60 mV and in a phasic (burst) mode from potentials negative to about -70 mV. An increase in current amplitude compensated the suppression of tonic firing much more readily than that of the burst firing on a low-threshold Ca2+ spike. Although a reduction in T-type Ca2+ channel activation may occur during isoflurane application, the depression of resonance is consistent with an interaction of a greatly increased leak conductance with the low-threshold Ca2+ current and the membrane capacitance. In the intact animal, this would tend to disrupt synchronized neural oscillations and the transfer of auditory information.