Table 2.
Roles of HCN channels in learning and memory of relevance to AD.
| Models | Main findings | References |
|---|---|---|
| HCN1-/- mice | As Ih decreases, the resting membrane potential became hyperactivated and input resistance increased significantly, resulting in further enhancement of the amplitude and duration of distal dendritic Ca2+ events. | Tsay et al., 2007 |
| HCN1-/- mice/HCN1f/f,cre mice | Theta activity was selectively enhanced in hippocampal CA1 pyramidal neurons. | Nolan et al., 2004 |
| HCN1f/f,cre mice | LTP was significantly enhanced at the direct perforant path input to the distal dendrites of CA1 pyramidal neurons, as was spatial learning and memory. | Nolan et al., 2004 |
| HCN2-/- mice | LTP was significantly enhanced. | Matt et al., 2011 |
| Mice with deletion of HCN2 from interneurons | LTP was significantly enhanced. | Matt et al., 2011 |
| HCN3-/- mice | There were no significant deficits in motor learning and spatial learning in comparison with control mice. | Stieglitz et al., 2017 |
| 2VO rats | Rats displayed a prolonged time to swim to the platform and altered expression patterns of HCN1 and HCN2 in the hippocampal CA1 area. Spatial learning and memory impairment could be improved when restoring the expression of HCN1 and HCN2. | Li et al., 2014; Luo et al., 2015 |
HCN1-/-, HCN1 knockout; HCN1f/f,cre, forebrain-restricted knockout; HCN2-/-, HCN2 knockout; HCN3-/-, HCN3 knockout; LTP, long-term potentiation; 2VO, permanent bilateral occlusion of the common carotid arteries.