Low-threshold calcium current and resonance in thalamic neurons: a model of frequency preference

1. We constructed a mathematical model of the subthreshold electrical behavior of neurons in the nucleus mediodorsalis thalami (MDT) to elucidate the basis of a Ni(2+)-sensitive low-frequency (2-4 Hz) resonance found previously in these neurons. 2. A model that included the low- and high-threshold Ca2+ currents (IT and IL), a Ca(2+)-activated K+ current (IC), a rapidly inactivating K+ current (IA), a voltage-dependent K+ current which we call IKx, and a voltage-independent leak current (Il), successfully simulated the low-threshold spike observed in MDT neurons. This model (the MDT model) and a minimal version of the model containing only IT and I1 (the minimal MDT model) were used in the analysis. 3. An impedance function was derived for a linearized version of the MDT model. This showed that the model predicts a low-frequency (2-4 Hz) resonance in the voltage response to "small" oscillatory current inputs (producing voltage changes of < 10 mV) when the membrane potential is between -60 and -85 mV. 4. Further examination of the impedances for the MDT and minimal MDT models shows that IT underlies the frequency- and voltage-dependent resonance. The slow inactivation of IT results in an attenuation of voltage responses to low frequencies, resulting in a band-pass behavior. The fast activation of IT amplifies the resonance and modulates the peak frequency but does not, in itself, cause resonance. 5. When voltage responses are small (< 10 mV), the strength and voltage-dependence of resonance of the minimal MDT model are determined by the steady-state window conductance, gw, due to IT. This steady-state conductance arises where the steady-state activation, m(infinity2)(V), and inactivation, h(infinity) (V), curves overlap. Parallel shifts in the inactivation curve can eliminate or enhance resonance with little effect on the IT-dependent low-threshold spike evoked after hyperpolarizing current pulses. When the peak magnitude of gw was large, the minimal MDT model showed spontaneous oscillations at 3 Hz with amplitudes > 30 mV. 6. Large oscillatory current inputs evoked significantly nonlinear voltage responses in the minimal MDT model, but the 2- to 4-Hz frequency selectivity (predicted from the linearized impedance) remained. 7. We conclude that the properties of the low-threshold Ca2+ current, IT, are sufficient to explain the Ni(2+)-sensitive 2- to 4-Hz resonance seen in MDT neurons.(ABSTRACT TRUNCATED AT 400 WORDS)