Increased Size and Stability of CA1 and CA3 Place Fields in HCN1 Knockout Mice

Hippocampal CA1 and CA3 pyramidal neuron place cells encode the spatial location of an animal through localized firing patterns called "place fields." To explore the mechanisms that control place cell firing and their relationship to spatial memory, we studied mice with enhanced spatial memory resulting from forebrain-specific knockout of the HCN1 hyperpolarization-activated cation channel. HCN1 is strongly expressed in CA1 neurons and in entorhinal cortex grid cells, which provide spatial information to the hippocampus. Both CA1 and CA3 place fields were larger but more stable in the knockout mice, with the effect greater in CA1 than CA3. As HCN1 is only weakly expressed in CA3 place cells, their altered activity likely reflects loss of HCN1 in grid cells. The more pronounced changes in CA1 likely reflect the intrinsic contribution of HCN1. The enhanced place field stability may underlie the effect of HCN1 deletion to facilitate spatial learning and memory.