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 Ni2+-sensitive low-frequency (2-4 Hz) resonance found previously in these neurons. 2. A model that included the low- and high-threshold Ca2+ currents (I-T and I-L), a Ca2+-activated K+ current(l(C)), a rapidly inactivating K+ current (I-A), a voltage-dependent K+ current which we call I-Kx,I- and a voltage-independent leak current (I-1), successfully simulated the low-threshold spike observed in MDT neurons. This model (the MDT model) and a minimal version of the model containing only I-T and I-T (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 I-T underlies the frequency- and voltage-dependent resonance. The slow inactivation of I-T results in an attenuation of voltage responses to low frequencies, resulting in a band-pass behavior. The fast activation of I-T 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, g(w,) due to I-T. This steady-state conductance arises where the steady-state activation, m(oo)(2)(V), and inactivation, h(oo)(V), curves overlap. Parallel shifts in the inactivation curve can eliminate or enhance resonance with little effect on the I-T-dependent low-threshold spike evoked after hyperpolarizing current pulses. When the peak magnitude of g(w) 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, I-T,I- are sufficient to explain the Ni2+-sensitive 2- to 4-Hz resonance seen in MDT neurons. We speculate that this frequency preference, expressed when neurons are hyperpolarized beyond -60 mV, may play a role in the organization of low-frequency activity in the thalamus during sleep.