Differential Expression of HCN Subunits Alters Voltage-Dependent Gating of h- channels in CA1 Pyramidal Neurons from the Dorsal and Ventral Hippocampus

1 2 The rodent hippocampus can be divided into dorsal (DHC) and ventral domains (VHC) 3 based on behavioral, anatomical, and biochemical differences. Recently, we reported 4 that CA1 pyramidal neurons from the VHC were intrinsically more excitable than DHC 5 neurons, but the specific ionic conductances contributing to this difference were not 6 determined. Here, we investigated the hyperpolarization-activated current (Ih) and the 7 expression of HCN1 and HCN2 channel subunits in CA1 pyramidal neurons from the 8 DHC and VHC. Measurement of Ih using cell-attached patches revealed a significant 9 depolarizing shift in the V1/2 of activation for dendritic h-channels in VHC neurons (but 10 not DHC neurons), and ultrastructural immunolocalization of HCN1 and HCN2 channels 11 revealed a significantly larger HCN1/HCN2 ratio for VHC neurons (but not DHC 12 neurons). These observations suggest that a shift in the expression of HCN1 and 13 HCN2 channels drives functional changes in Ih for VHC neurons (but not DHC neurons), 14 and could thereby significantly alter the capacity for dendritic integration of these 15 neurons. 16 17 18 Word Count: 160 19 20 21