Isoflurane Attenuates Resonant Responses of Auditory Thalamic Neurons

Tennigkeit, Frank, Craig R. Ries, Dietrich W. F. Schwarz, and Ernest Puil. Isoflurane attenuates resonant responses of auditory thalamic neurons. J. Neurophysiol. 78: 591–596, 1997. 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 ∼1 Hz), reducing the peak impedance more than the magnitudes at other frequencies. At concentrations of ≥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 activationmay 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.