Modulation of frequency selectivity by Na +- and K +-conductances in neurons of auditory thalamus

Abstract

In thalamic neurons, frequency-filter properties arise from intrinsic membrane properties which transform sensory inputs to thalamocortical signals. They also contribute to the tendency for the membrane to generate synchronized oscillations. We studied the frequency selectivities of thalamocortical neurons in the rat ventral medial geniculate body (MGBv) in vitro, using whole-cell recording techniques, sinewave (swept `ZAP' or single) current inputs and pharmacological blockade of membrane currents. In a voltage range that was subthreshold to spike genesis, the frequency responses below 20 Hz were voltage-dependent; they exhibited lowpass characteristics at depolarized potentials and bandpass resonance (near 1 Hz) in the activation range (∼−65 to −50 mV) of the low-threshold Ca 2+-current ( I T). A temperature increase of >10°C in 3 neurons did not change this voltage-dependence and increased the frequency of maximum resonance to 2 Hz. The removal of extracellular Ca 2+, its equimolar substitution with Mg 2+ or blockade of I T with Ni 2+ (0.5 mM) completely blocked the resonance at hyperpolarized potentials or rest, as well as the low-threshold Ca 2+-spike (LTS). Blockade of high threshold Ca 2+-currents with Cd 2+ (50 μM) did not affect the resonance. These data implied that, like the LTS, an activation of I T produced the membrane resonance. An increased ZAP-current input evoked action potentials near the resonant frequency as well as Cd 2+-sensitive high-threshold Ca 2+-spikes at depolarized membrane potentials and very low frequencies. By blocking a persistent Na +-current ( I NaP), tetrodotoxin (300 nM) reduced the magnitude of the frequency response without affecting the frequency preference. The response was larger in amplitude, especially at frequencies lower than the maximum resonant frequency, when we used 4-aminopyridine (0.05–0.1 and 1–2 mM), Ba 2+ (0.2 mM) or Cs + (3 mM) to block voltage-dependent K +-currents. From these data, we suggest that A-type ( I A and I As) and inwardly rectifying ( I KIR) K +-currents modulate resonance, changing the quality of the lowpass filter function. We conclude that the generation of membrane resonance in MGBv neurons depends critically on I T-activation while the quality of the frequency response is subject to modulation by voltage-dependent conductances. The frequency selectivities in MGBv may contribute to lowpass filter functions for auditory transmission during wakefulness and oscillations observed during sleep.