Aims: 

Thalamocortical (TC) neurons from intralaminar thalamic nuclei possess unusual bursting behavior. To determine the possible contribution of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels to this firing property, we analyzed the voltage-dependency and cAMP-sensitivity of hyperpolarization-activated inward currents (I_h) in TC neurons from intralaminar nuclei (IL) and the somatosensory ventrobasal thalamic complex (VB).

Methods: 

Whole-cell patch-clamp recordings were performed on thalamic slices from wild type (WT) and HCN4-deficient mice (HCN4^-/-).

Results: 

TC neurons revealed significantly different I_h amplitudes at –130 mV in WT (IL: 469 ± 46 pA, n = 11; VB: 831 ± 112 pA, n = 11) and HCN4^-/- (IL: 89 ± 8 pA, n = 26; VB: 225 ± 11 pA, n = 14). Furthermore, while the kinetics of I_h activation were best approximated by a bi-exponential function in all WT as well as HCN4^-/- VB neurons, IL neurons from HCN4^-/- revealed mono-exponential kinetics. Fast activation in HCN4^-/- was accompanied by a reduction in cAMP-sensitivity. In WT neurons, 10 mM intracellular cAMP positively shifted I_h activation curves by 10 and 5 mV in VB and IL neurons, respectively. In HCN4^-/- however, the cAMP effect was reduced in VB (+7 mV shift) and nearly abolished in VB (+2 mV shift).

Conclusions: 

These findings indicate that I_h in IL and VB neurons is mostly carried by HCN4. In addition, I_h in HCN4^-/- seems to be carried by HCN1/HCN2 in VB, and exclusively by HCN1 in IL neurons.