TY - JOUR
T1 - Low-threshold calcium current and resonance in thalamic neurons
T2 - A model of frequency preference
AU - Hutcheon, B.
AU - Miura, R. M.
AU - Yarom, Y.
AU - Puil, E.
PY - 1994
Y1 - 1994
N2 - 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 (I(C)), a rapidly inactivating K+ current (I(A)), a voltage-dependent K+ current which we call I(Kx), and a voltage-independent leak current (I(I)), 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 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 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∞/2 (F), and inactivation, h∞ (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), 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.
AB - 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 (I(C)), a rapidly inactivating K+ current (I(A)), a voltage-dependent K+ current which we call I(Kx), and a voltage-independent leak current (I(I)), 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 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 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∞/2 (F), and inactivation, h∞ (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), 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.
UR - http://www.scopus.com/inward/record.url?scp=0027983016&partnerID=8YFLogxK
U2 - 10.1152/jn.1994.71.2.583
DO - 10.1152/jn.1994.71.2.583
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C2 - 8176427
AN - SCOPUS:0027983016
SN - 0022-3077
VL - 71
SP - 583
EP - 594
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
IS - 2
ER -